methimazole and Body-Weight

This review of thyroid influence on body growth in poultry is organized around the following parameters of growth: increase in body weight and skeletal size, muscle growth, and growth of cartilage and bone. The greatest effect of goitrogens on growth of embryos occurs during late embryogenesis at a time when normal thyroid hormone levels are increasing. Posthatching growth is reduced in severely hypothyroid animals, and body weight gain is affected more than bone growth. Thyroid hormone replacement restores body growth of thyroidectomized chickens, but supplemental hormone in normal animals has no beneficial effect on growth. Excessive T3 (fed at 1 ppm) is detrimental to growth and feed efficiency. No clear correlation between thyroid hormone concentration and growth rate of normal chickens has been identified. Growth depression in sex-linked dwarf birds is at least partially reversed by supplemental T3. Muscle growth is reduced in goitrogen-treated chickens and the growth reduction is reversed by supplemental thyroxine. Total DNA accumulation is reduced in hypothyroid chickens, but muscle mass relative to DNA content is normal following long-term treatment; this suggests some regulation of muscle mass relative to DNA content. T3 increases the number of muscle fiber nuclei in hypothyroid chickens and the uptake of 3H-thymidine into nuclei within the basal lamina. T3 directly stimulates growth and maturation of embryonic chick cartilage and enhances the in vitro action of somatomedins on cartilage growth. There is little information concerning the role of the thyroid in posthatching cartilage and bone growth in poultry.

Topics: Animals; Body Weight; Bone and Bones; Bone Development; Cartilage; Chick Embryo; Chickens; DNA; Growth Hormone; Methimazole; Muscle Development; Muscles; Thyroid Gland; Thyroxine; Triiodothyronine

Topics: Adult; Animals; Antithyroid Agents; Basolateral Nuclear Complex; Body Weight; Brain-Derived Neurotrophic Factor; Cyclic AMP Response Element-Binding Protein; Depression, Postpartum; Disease Models, Animal; Estradiol; Female; Humans; Methimazole; Mice; Neurons; Neuroprotection; Postpartum Period; Progesterone; Progestins; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Diabetes and hypothyroidism produce adverse effects on body weight and sexual maturity by inhibiting body growth and metabolism. The occurrence of diabetes is always accompanied with thyroid dysfunction. Thus, it is important to take hypo- or hyper-thyroidism into consideration when exploring the adverse effects caused by diabetes. Previous reports have found hypothyroidism inhibits testicular growth by delaying Sertoli cell differentiation and proliferation. Hence, by establishing a mouse model of diabetes combined with hypothyroidism, we provided evidence that poly glandular autoimmune syndrome affected testicular development and spermatogenesis.. we mimicked polyglandular deficiency syndrome in both immature and prepubertal mice by induction of diabetes and hypothyroidism, which caused decreases in serum concentrations of testosterone and insulin like growth factor 1 (IGF-1). Such reduction of growth factor resulted in inhibition of testicular and epididymal development. Moreover, expressions of Claudin-11 were observed between Sertoli cells and disrupted in the testes of syndrome group mice. We also found reduced sperm count and motility in prepubertal mice.. This mimicry of the diabetes and thyroid dysfunction, will be helpful to better understand the reasons for male infertility in diabetic-cum-hypothyroid patients.

Topics: Animals; Blood Glucose; Blood-Testis Barrier; Body Weight; Claudins; Diabetes Mellitus; Epididymis; Female; Hypothyroidism; Insulin-Like Growth Factor I; Male; Methimazole; Mice, Inbred ICR; Organ Size; Seminiferous Tubules; Sperm Motility; Spermatogenesis; Streptozocin; Testosterone

Maternal obesity is a risk factor for offspring obesity. The melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. The present study examined the epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in the offspring of high-fat diet (HFD)-induced obese dams and sought to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed an HFD or standard chow from weaning through gestation and lactation. Epigenetic alterations were analyzed in the offspring on postnatal day 21 at the Mc4r promoter using chromatin immunoprecipitation and bisulfite sequencing. To study the role of triiodothyronine (T3) in Mc4r downregulation, dams received methimazole (MMI), an inhibitor of thyroid hormone production. Offspring of HFD-fed dams had a greater body weight, elevated plasma T3 concentrations, and lower Mc4r messenger RNA levels than controls. At the Mc4r promoter, offspring of HFD-fed mothers demonstrated increased histone 3 lysine 27 acetylation (H3K27ac) with a greater association to thyroid hormone receptor-β (TRβ), an inhibitor of Mc4r transcription. Moreover, TRβ coimmunoprecipitated with H3K27ac, supporting their presence in the same complex. Maternal MMI administration prevented the HFD reduction in Mc4r levels, the increase in TRβ, and the increase in the TRβ-H3K27ac association, providing further support for the role of T3 in downregulating Mc4r levels. These findings demonstrate that a perinatal HFD environment affects Mc4r regulation through a T3 metabolic pathway involving histone acetylation of its promoter.

Topics: Animals; Body Weight; Eating; Epigenesis, Genetic; Female; Maternal Nutritional Physiological Phenomena; Methimazole; Obesity; Pregnancy; Promoter Regions, Genetic; Rats; Rats, Wistar; Receptor, Melanocortin, Type 4; Triiodothyronine

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development.

Topics: Acoustic Stimulation; Acoustics; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antithyroid Agents; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Hearing Loss; Hypothyroidism; Methimazole; Rats; Rats, Wistar; Reflex, Startle; Thyroid Hormones; Vocalization, Animal

The aim of this study was to investigate depression-like behaviors of juvenile rats with congenital and postnatal hypothyroidism.. Twenty-seven newborn rat pups were used. First, 6-month-old Wistar Albino female rats were impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day of pregnancy until postnatal 21 days (P21) to generate pups with congenital hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10), methimazole was given from P0 to P21. In the control group (n=9), dam rats were fed ad libitum and normal tap water. Offspring were fed with breast milk from their mothers. The behavioral parameters were measured with the juvenile forced swimming test (JFST). The procedure of JFST consisted of two sessions in two consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2.. Increased immobility and decreased climbing duration were observed in both congenital and postnatal hypothyroidism groups. Decreased swimming duration was detected in the postnatal hypothyroidism group. Both hypothyroidism groups had a lower body weight gain compared with the control group, while the congenital hypothyroidism group had the lowest body weight.. Our results showed that hypothyroidism had negative effects on depression-like behavior as well as on growth and development. Both congenital and postnatal hypothyroidism caused an increase in immobility time in JFST. New studies are required to understand the differing results on depression-like behavior between congenital and postnatal hypothyroidism.

Topics: Analysis of Variance; Animals; Animals, Newborn; Body Weight; Congenital Hypothyroidism; Depression; Female; Hypothyroidism; Male; Methimazole; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Swimming; Thyroxine; Time Factors; Triiodothyronine

Subclinical hypothyroidism (SCH) and its associations with atherosclerosis (AS) and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4) administration affects these changes.. In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4). The SCH rats were induced by administration of 10 mg x kg(-1) x d(-1) methimazole (MMI) once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg x kg(-1) x d(-1) L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage.. The SCH group had significantly higher thyroid-stimulating hormone (TSH), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) levels and a lower nitric oxide (NO) level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries.. These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.

Topics: Animals; Aorta; Blood Pressure; Body Weight; Cholesterol; Cholesterol, LDL; Disease Models, Animal; Endothelins; Hemodynamics; Hypothyroidism; Male; Methimazole; Nitric Oxide; Rats; Rats, Wistar; Thyroxine

Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status.. To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions.. Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum.. Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes.. The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

Topics: Animals; Antioxidants; Benzene Derivatives; Body Weight; Cerebral Cortex; Corpus Callosum; Disease Models, Animal; Female; Hippocampus; Hypothyroidism; Lipid Peroxidation; Methimazole; NF-E2-Related Factor 2; Organoselenium Compounds; Oxidative Stress; Random Allocation; Rats, Wistar; Reactive Oxygen Species; RNA, Messenger; Sulfhydryl Compounds

The thyroid hormone triiodothyronine (T3) is known to affect energy balance. Recent evidence points to an action of T3 in the hypothalamus, a key area of the brain involved in energy homeostasis, but the components and mechanisms are far from understood. The aim of this study was to identify components in the hypothalamus that may be involved in the action of T3 on energy balance regulatory mechanisms.. Sprague Dawley rats were made hypothyroid by giving 0.025% methimazole (MMI) in their drinking water for 22 days. On day 21, half the MMI-treated rats received a saline injection, whereas the others were injected with T3. Food intake and body weight measurements were taken daily. Body composition was determined by magnetic resonance imaging, gene expression was analyzed by in situ hybridization, and T3-induced gene expression was determined by microarray analysis of MMI-treated compared to MMI-T3-injected hypothalamic RNA.. Post mortem serum thyroid hormone levels showed that MMI treatment decreased circulating thyroid hormones and increased thyrotropin (TSH). MMI treatment decreased food intake and body weight. Body composition analysis revealed reduced lean and fat mass in thyroidectomized rats from day 14 of the experiment. MMI treatment caused a decrease in circulating triglyceride concentrations, an increase in nonesterified fatty acids, and decreased insulin levels. A glucose tolerance test showed impaired glucose clearance in the thyroidectomized animals. In the brain, in situ hybridization revealed marked changes in gene expression, including genes such as Mct8, a thyroid hormone transporter, and Agrp, a key component in energy balance regulation. Microarray analysis revealed 110 genes to be up- or downregulated with T3 treatment (± 1.3-fold change, p<0.05). Three genes chosen from the differentially expressed genes were verified by in situ hybridization to be activated by T3 in cells located at or close to the hypothalamic ventricular ependymal layer and differentially expressed in animal models of long- and short-term body weight regulation.. This study identified genes regulated by T3 in the hypothalamus, a key area of the brain involved in homeostasis and neuroendocrine functions. These include genes hitherto not known to be regulated by thyroid status.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Eating; Energy Metabolism; Gene Expression Regulation; Homeostasis; Hypothalamus; Hypothyroidism; Male; Methimazole; Rats; Rats, Sprague-Dawley; Triiodothyronine

Thyroid hormones (THs) are essential for proper brain development in mammals. TH insufficiency during early development causes structural and functional abnormalities in brain leading to cognitive dysfunction. The specific effects of developmental hypothyroidism on attention have not been well characterized in animal models. The present study was conducted to characterize the effects of developmental hypothyroidism on attention in rats, and tested the hypothesis that the hypothyroidism has adverse impacts on attention by means of a visual signal detection task. Pregnant rats were exposed to the anti-thyroid drug, methimazole (0.02% w/v) via drinking water from gestational day 15 through postnatal day (PND) 21 to induce maternal and neonatal hypothyroidism. Male offspring served as subjects for the task started on PND 90. A light stimulus (500 ms, 250 ms or 50 ms) was presented in signal trials and not in blank trials. The offspring were required to discriminate these signal events, and subsequently press the correct lever. The correct response for signal and non-signal events was considered as hit and correct rejection, respectively. The hypothyroid offspring exhibited a decreased hit response for short signals (250 ms and 50 ms) which requires the higher attentional demand. The total number of lever responses during inter-trial interval (ITI) was also increased in the hypothyroid group. The number of lever responses was negatively correlated with a hit response at 50 ms, not at 250 ms. These results suggest that developmental hypothyroidism disrupts signal detection performance via impairment of visual attention and the altered lever response behavior.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antithyroid Agents; Attention; Body Weight; Conditioning, Operant; Female; Hypothyroidism; Male; Methimazole; Perceptual Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Reaction Time; Reinforcement, Psychology; Signal Detection, Psychological

To evaluate weight change during hyperthyroidism treatment, and to correlate it with IL-6 and TNF-alpha concentrations.. Forty two patients were included. Body weight (BW), body mass index (BMI), clinical and laboratory characteristics were recorded. IL-6 and TNF-alpha were determined before treatment with methimazole (MMI) and in euthyroidism.. BW was 59.62 ± 11.5 kg in hyperthyroidism, and 69.91 ± 14.4 kg in euthyroidism (p < 0.001). BMI increased from 23.1 ± 3.8 kg/m(2) to 27 kg/m(2) ± 4.7 during treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m(2) and 33.3%, BMI > 25 kg/m(2). In euthyroidism, 38% of patients had BMI < 25 kg/m(2) and 62%, BMI > 25 kg/m(2) (p = 0.01). In euthyroidism, we found a significant reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6 and TNF-alpha, and BW or BMI.. An important increase in BW and BMI was observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations were only related with return to euthyroidism.

Topics: Adult; Antithyroid Agents; Body Mass Index; Body Weight; Female; Graves Disease; Humans; Hyperthyroidism; Interleukin-6; Male; Methimazole; Thyroid Gland; Thyroid Hormones; Tumor Necrosis Factor-alpha; Weight Gain

We evaluated the contribution of the thyroid hormones to the long-term maintenance of feeding behavior and body weight, while distinguishing their direct central effects from those resulting from the metabolic rate in the peripheral tissues.. We assessed the effect of hypothyroidism on the long-term (6 months) regulation of food intake, body weight, and energy expenditure in rats. We then generated the recovery of a euthyroid condition in the brain while maintaining a low T3 availability for the peripheral organs, i.e. a combined condition of central euthyroidism with peripheral hypothyroidism, with the aid of a pharmacological combination.. Hypothyroidism caused a decrease in the daily food intake, body weight, and body temperature. The food intake and body temperature stabilized at a lower value, whereas body weight kept decreasing at a constant rate. The administration of exogenous T4 increased food intake and body-weight gain, but had no effect on body temperature.. The thyroid hormones are necessary for the long-term regulation of energy intake, storage, and expenditure by different mechanisms. The feeding behavior seems to be partially dependent on a direct action of the thyroid hormones on the brain and this effect is independent of the energy expenditure in the peripheral organs. The body weight is closely dependent on the thyroid status and its maintenance seems to involve thyroid action on mechanisms other than feeding and metabolic rate.

Topics: Animals; Antithyroid Agents; Body Temperature; Body Weight; Brain Chemistry; Eating; Energy Metabolism; Hypothalamus; Hypothyroidism; Male; Methimazole; Rats; Rats, Wistar; Thyroxine; Time Factors; Triiodothyronine

This study aims to investigate the improving effects of selenium on methimazole-induced kidney impairments in adult rats and their pups. The animals were randomly divided into four groups of six each: group I served as control which received standard diet; group II received only methimazole in drinking water as 250 mg/l; group III received both methimazole (250 mg/l, orally) and selenium (0.5 mg/kg of diet); group IV served as a positive control and received selenium (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatments were started from the 14th day of pregnancy until day 14 after delivery. In the methimazole-treated group, body and absolute kidney weights decreased in pups and their mothers when compared to control. Daily urine volume, plasma creatinine levels were higher, while urinary levels were lower than in control. Besides, antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high kidney malondialdehyde levels, while those of plasma and urinary uric acid showed a significant decline. Methimazole-treated rat kidneys exhibited leucocytic infiltrations, vascular congestion and narrowed Bowman's space. Co-administration of selenium through diet improved all the parameters cited above in adult rats and their progeny. Nevertheless, the distorted histoarchitecture in rat kidney was alleviated by selenium treatment. It can then be concluded that selenium is an important protective element that may be used as a dietary supplement against kidney impairments.

Topics: Animals; Animals, Newborn; Antioxidants; Antithyroid Agents; Biomarkers; Body Weight; Female; Kidney; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Maternal Exposure; Methimazole; Organ Size; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Sodium Selenite; Vitamin E

Little information is available about changes in body weight and body mass index in children before, during, and after treatment for Graves' disease (GD).. Our objective was to examine changes in body weight after treatment for GD in children as related to clinical features.. The medical records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0-18.5 (mean 10.9) yr] were examined. Patients were included if clinical data were available for 1 yr before and after the diagnosis of GD.. Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were assessed.. Overall, patients presented with an average BMI z-score of -0.02 ± 1.05 that was not different from the normal population (P = 0.921) or their premorbid values (P = 0.07). However, in the subset of patients who were initially overweight or obese in the premorbid state, the BMI decreased significantly during the development of hyperthyroidism (P < 0.05). After initiation of treatment, patients gained significant amounts of weight over the first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in BMI persisted in about 25% of the patients.. Excessive weight gain within 6 months of treatment is seen in children treated for GD, and the gain in weight can persist.

Topics: Adolescent; Aging; Antithyroid Agents; Body Mass Index; Body Weight; Child; Child, Preschool; Cohort Studies; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Propylthiouracil; Sex Characteristics; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy; Weight Gain

In experiences on 108 male rats, the effect of acute (immobilization during 3 hrs) and chronic (immobilization for 3 hrs during 5 days) stresses on the organism general stability was studied as evaluated with changes of body weight, adrenal glands, spleen, thymus relative mass, gastric mucosa state, animals physical endurance. Chronic stress evoked more obvious decreasing of spleen and thymus relative mass than the acute one, as well as lesion of gastric mucosa accompanied with decrease of the rat resistance to physical loading. Thyroid function suppression by merkazolil (1.2 mg/100 g body weight during 14 days) promotes further the reduction of the organism stability in acute and, especially, in chronic stress, while physiological doses of thyroid hormones (5.0-8.0 mcg of thyroxin on kg of body weight during 28 days), on the contrary, increased it in both stress conditions. Existence of the organism stability dependence on thyroid status both in acute and chronic stress proves iodothyronine's important role in the organism antistress-system.

Topics: Adrenal Glands; Animals; Antithyroid Agents; Body Weight; Gastric Mucosa; Male; Methimazole; Organ Size; Physical Endurance; Rats; Spleen; Stress, Psychological; Thymus Gland; Thyroid Gland

Thyroid hormones play important roles in vertebrate brain development. However, there is little understanding of the direct effects of fetal thyroid dysfunction, i.e., not acquired through the mother, on learning ability. In the present study, we use a chick embryo as a fetal model to investigate the effects of prenatal exposure to antithyroid drugs on imprinting behavior in hatched chicks. Methimazole (MMI) at 20micromol/egg or 5micromol/egg of propylthiouracil (PTU) was administered to eggs on day 14 while the control was given only a vehicle. An imprinting test was conducted after the chicks hatched. Day-old chicks were exposed to a rotating training object for 150min. The next day, the trained chicks were exposed to the training object and a novel object. The imprinting preference was represented as a preference score (PS) calculated as the rate of following the training object to following the training and novel objects. In the MMI-treated chicks, the PS was 0.68+/-0.06 (range, 0.38-0.88), which was significantly lower than that in the control chicks (0.86+/-0.04, p<0.01). In the PTU-treated chicks, the PS was 0.69+/-0.04 (range, 0.52-0.89), which was also significantly lower than that in the control (0.88+/-0.02, p<0.001). The present findings suggested that fetal thyroid dysfunction inhibited brain development, leading to impaired learning and memory. Our chick model can be considered useful for investigating the direct effects of prenatal exposure to antithyroid drugs or substances in the environment on learning ability after birth.

Topics: Age Factors; Animals; Antithyroid Agents; Birth Rate; Body Weight; Chick Embryo; Chickens; Dose-Response Relationship, Drug; Female; Imprinting, Psychological; Methimazole; Organ Size; Propylthiouracil; Thyroid Gland; Time Factors

The effects of thyroid hormone (TH) status on energy metabolism and tissue-specific substrate supply in vivo are incompletely understood. To study the effects of TH status on energy metabolism and tissue-specific fatty acid (FA) fluxes, we used metabolic cages as well as (14)C-labeled FA and (3)H-labeled triglyceride (TG) infusion in rats treated with methimazole and either 0 (hypothyroidism), 1.5 (euthyroidism), or 16.0 (thyrotoxicosis) microg per 100 g/d T(4) for 11 d. Thyrotoxicosis increased total energy expenditure by 38% (P = 0.02), resting energy expenditure by 61% (P = 0.002), and food intake by 18% (P = 0.004). Hypothyroidism tended to decrease total energy expenditure (10%; P = 0.064) and resting energy expenditure (12%; P = 0.025) but did not affect food intake. TH status did not affect spontaneous physical activity. Thyrotoxicosis increased fat oxidation (P = 0.006), whereas hypothyroidism decreased glucose oxidation (P = 0.035). Plasma FA concentration was increased in thyrotoxic but not hypothyroid rats. Thyrotoxicosis increased albumin-bound FA uptake in muscle and white adipose tissue (WAT), whereas hypothyroidism had no effect in any tissue studied, suggesting mass-driven albumin-bound FA uptake. During thyrotoxicosis, TG-derived FA uptake was increased in muscle and heart, unaffected in WAT, and decreased in brown adipose tissue. Conversely, during hypothyroidism TG-derived FA uptake was increased in WAT in association with increased lipoprotein lipase activity but unaffected in oxidative tissues and decreased in liver. In conclusion, TH status determines energy expenditure independently of spontaneous physical activity. The changes in whole-body lipid metabolism are accompanied by tissue-specific changes in TG-derived FA uptake in accordance with hyper- and hypometabolic states induced by thyrotoxicosis and hypothyroidism, respectively.

Topics: Adipose Tissue, White; Albumins; Animals; Antithyroid Agents; Body Weight; Carbon Radioisotopes; Eating; Energy Metabolism; Fatty Acids; Homeostasis; Lipid Metabolism; Male; Methimazole; Motor Activity; Muscles; Oxidation-Reduction; Rats; Rats, Wistar; Thyroid Hormones; Triglycerides; Tritium

The effects of hypothyroidism on lipid peroxidation (LP), reactive oxygen species (ROS), and nitric oxide synthase (NOS), levels and expression, in rat brain were examined. Hypothyroidism was induced by administering methimazole in drinking water (60 mg/kg/day). In striatum, motor cortex and cerebellum of hypothyroid rats LP was not modified, whereas LP and ROS increased in amygdala and hippocampus of hypothyroid rats at the third week of treatment with methimazole as compared to euthyroid group values. Regarding NOS participation, only hippocampal constitutive-NOS activity was increased, accompanied by an augmentation in nNOS expression. Results show that hypothyroidism induces selective oxidative stress in both the hippocampus and amygdala, where the nitrergic system is involved.

Topics: Amygdala; Animals; Antithyroid Agents; Body Temperature; Body Weight; Hippocampus; Hypothyroidism; Lipid Peroxidation; Male; Methimazole; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T(4)) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology...). Besides, T(4) induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.

Topics: Acrylamide; Adrenal Medulla; Animals; Body Weight; Female; Methimazole; Mice; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Thyroxine

To investigate the effect of hypothyroidism on gonadal and adrenal functions in male Japanese quail (Coturnix japonica), hypothyroidism was induced in male adult Japanese quail by daily administration of 2-Mercapto-1-methylimidazole (methimazole) in their drinking water. Four weeks after methimazole treatment, the Japanese quail were sacrificed, and the plasma concentrations of free triiodothyronine (FT3), free thyroxine (FT4), total T3 (TT3), total T4 (TT4), corticosterone, testosterone, LH and immunoreactive (ir) inhibins were measured by radioimmunoassay, the testes and adrenal glands were removed and weighed and the thyroid glands and testes were fixed in 4% paraformaldehyde for histological observation. The results showed that the hypothyroidism induced by methimazole caused a significant decrease in body and testes weight; the plasma levels of FT3, FT4 and TT4 significantly decreased, and the hypothyroid quail possessed a greater number of small follicles and more follicular epithelial cells in the thyroid gland. In addition, hypothyroidism resulted in a significant decrease in the plasma concentrations of corticosterone, LH, testosterone and ir-inhibin. Furthermore, no spermatogenesis was found in the seminiferous tubules of the methimazole treatment groups. These results clearly demonstrate that hypothyroidism caused both gonadal and adrenal disturbances in the adult male Japanese quail.

Topics: Adrenal Glands; Age Factors; Animals; Antithyroid Agents; Body Weight; Coturnix; Hypothyroidism; Male; Methimazole; Organ Size; Testis; Thyroid Hormones

We designed three experiments to determine both the optimal dose of and time on experiment for methimazole (MMI; 1-methyl-2-mercaptimidazole). Our goals were to determine if chicken growth was related to thyroid hormone levels and if intermediary metabolism changed along with changes in thyroid hormone levels. Initiating MMI at one week of age decreased (P<0.01) plasma thyroid levels and growth in four-week old birds. In contrast, initiating MMI at two and three weeks of age decreased (P<0.05) hormone levels without affecting growth as severely. Although initiating MMI at two weeks of age depressed (P<0.05) plasma thyroid hormones at four weeks, there was little change in vitro lipogenesis at four weeks. Again, initiating MMI at one week of age decreased body weight, plasma thyroid hormones and in vitro lipogenesis at four weeks of age. In addition, this treatment also decreased (P<0.05) malic enzyme activity at this same age period. The second experiment showed that MMI, initiated at 14 days, had no significant effect on 28-day body weight and again decreased both plasma T(3) and T(4) but T(3) replacement increased plasma T(3) in both 14-28-day treatment groups. All body weights were similar at 30 days, however. Lastly, diets containing graded levels of MMI decreased thyroid hormones and body weight (0>0.25>0.5>1 g MMI/kg). In contrast, only the two higher levels (0.5 and 1 g MMI/kg) decreased in vitro lipogenesis. Growth depression, caused by MMI feeding, can occur without changes in lipid metabolism. The length of MMI administration may be as important as dose level in obtaining effects (growth, thyroid hormone depression and inhibition of lipogenesis).

Topics: Animals; Antithyroid Agents; Body Weight; Chickens; Dose-Response Relationship, Drug; Lipogenesis; Liver; Male; Methimazole; Thyroid Gland; Thyroxine; Triiodothyronine

The effect of hypothyroidism induced by thiamazole on the toxicity of amitriptyline was studied in chick embryos. Fertilized eggs of White Leghorns were incubated and investigated. 1.2 mg/0.2 ml/egg of thiamazole was injected into the albumen of fertilized eggs on the 9th day of incubation. The control group was given 0.2 ml/egg of physiological saline in the same manner. Amitriptyline at 1 mg/egg was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the injection of amitriptyline into the thiamazole-treated eggs, the heart rate was significantly decreased compared with the untreated eggs. These findings indicate that hypothyroidism induced by thiamazole has a marked influence on the toxicity of amitriptyline in chick embryos.

Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Antithyroid Agents; Body Weight; Chick Embryo; Electrocardiography; Heart Rate; Hypothyroidism; Methimazole

The effect of the hypothyroidism induced by thiamazole on toxic interactions between propranolol and disopyramide were studied in chick embryos. Fertilized eggs of White Leghorns were incubated and investigated. 1.2 mg/0.2 ml/egg of thiamazole was injected into the albumen of fertilized eggs on the 9th day of incubation. The control group was given 0.2 ml/egg of physiological saline in the same manner. Propranolol at 0.1 mg/egg and disopyramide at 0.3 mg/egg were injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the injection of propranolol and disopyramide into the thiamazole treated eggs, the heart rate was significantly decreased compared with the thiamazole untreated eggs. These findings indicate that hypothyroidism induced by thiamazole has a marked influence on the toxic interaction between propranolol and disopyramide in chick embryos.

Topics: Animals; Antithyroid Agents; Body Weight; Chick Embryo; Disopyramide; Drug Interactions; Hypothyroidism; Methimazole; Propranolol

Thyroid hormone has been reported to affect renal function. To investigate the effects of thyroid hormone on the progression of renal deterioration, thyroid hormone (dried thyroid) and an antithyroid drug (thiamazole) were administered to adriamycin (ADR)-induced renal failure rats. The rats were divided into four groups, including 1) ADR-DT, given dried thyroid and thiamazole; 2) ADR-T, given thiamazole; 3) ADR; and 4) control. The survival rate at the end of the study (22 weeks) was 62.5% in ADR-DT group and 100% in ADR-T, ADR, and control groups, respectively. There was a significant difference in the body weight and pulse rate between ADR-DT and ADR-T or ADR groups, except for the pulse rate at week 6 (P<0.05). The creatinine clearance was greater in the ADR-T group than in the ADR or ADR-DT groups at week 22, and was significantly different between the ADR-T and the ADR-DT groups (P<0.05). The fractional kidney weight and tubular changes were significantly greater in the ADR-DT group than in the ADR-T or ADR groups (P<0.05). The interstitial volume was significantly greater in the ADR-DT group than in the ADR-T group (P<0.05). We therefore conclude that a dried thyroid has an aggravative effect in the tubular changes and relative interstitial volume induced by ADR.

Topics: Animals; Biopsy, Needle; Blood Pressure Determination; Body Weight; Disease Models, Animal; Doxorubicin; Drug Interactions; Female; Heart Rate; Immunohistochemistry; Kidney Failure, Chronic; Kidney Function Tests; Male; Methimazole; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Risk Factors; Sensitivity and Specificity; Survival Rate; Thyroid Hormones

Sustained hyperleptinemia induced in normal rats causes the rapid disappearance of body fat. This is attributed to a marked increase in uncoupled fatty acid oxidation in the white adipocytes, which also occurs in hyperthyroidism. Because hyperleptinemic rats have normal plasma T3 or T4 levels, we tested the possibility of "localized hyperthyroidism" due to increased conversion of T4 to T3 in the adipose tissue. We therefore induced sustained hyperleptinemia in normal rats by intravenous injection of recombinant adenovirus containing the leptin cDNA (AdCMV-leptin) and measured the mRNA and the activity of enzymes involved in T4 metabolism in the disappearing fat. The epididymal fat pad remnants exhibited a decrease in mRNA of deiodinase 1 and a doubling of deiodinase 2 mRNA (p<0.05), but their enzyme activities did not differ from normoleptinemic controls. To determine if thyroid hormone was required for the fat-wasting action of hyperleptinemia, we infused AdCMV-leptin into rats made athyroid by total thyroidectomy or by methimazole therapy. The fat loss in hyperleptinemic athyroid rats was as great as in euthyroid controls. We conclude that the fat-wasting effect of sustained hyperleptinemia does not involve "local hyperthyroidism" in white adipose tissue and does not require thyroid hormone.

Topics: Adipose Tissue; Animals; Body Weight; DNA, Complementary; Fats; Fatty Acids; Iodide Peroxidase; Leptin; Male; Methimazole; Oxygen; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Hormones; Thyroxine; Triiodothyronine

Hindlimb ischemia for 4 h, followed by reperfusion, resulted in necrosis of most soleus muscle in euthyroid rats, whereas only slight damage occurred in hypothyroid rats. Muscle repair after transection of the tibialis anterior muscle of hypothyroid rats showed delayed debris removal, initial retardation of myotube formation, and a higher incidence of aberrant sarcomeres in newly formed muscle fibers by electron microscopy. The protective mechanism against ischemia in hypothyroid muscles can probably be attributed to decreased degradation of high-energy phosphates, reduced formation of substrates for xanthine oxidase during ischemia, and attenuated generation of harmful oxygen free radicals during reperfusion. Initial delay of myotube formation seems to reflect retarded proliferation of muscle precursor cells. Prolonged occurrence of aberrant sarcomeres in hypothyroidism is perhaps due to a delay or imbalance in the synthesis of proteins that assemble sarcomeres. These findings demonstrate the significant roles of thyroid hormones in ischemic injury and muscle repair.

Topics: Animals; Antithyroid Agents; Body Weight; Hindlimb; Hypothyroidism; Ischemia; Male; Methimazole; Microscopy, Electron; Muscle Fibers, Skeletal; Muscle, Skeletal; Rats; Rats, Wistar; Regeneration; Thyroid Gland; Wound Healing

The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4 degrees C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Antithyroid Agents; Body Weight; Carrier Proteins; Cold Temperature; Female; Glyceraldehyde-3-Phosphate Dehydrogenases; Hypothyroidism; Ion Channels; Isoenzymes; Male; Membrane Proteins; Methimazole; Mitochondria; Mitochondrial Proteins; Oxygen Consumption; Rats; Rats, Wistar; RNA, Messenger; Thermogenesis; Thyroid Gland; Time Factors; Uncoupling Protein 1

We examined the contribution of hypothyroidism to streptozotocin diabetes-induced alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero-flow ischaemia. Diabetic rats received either protamine zinc insulin (10 IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min main left coronary artery occlusion, followed by 30-min reperfusion. Serum free thyroxine concentrations, rectal temperature and ex vivo heart rate were significantly decreased in the 8-week diabetic group (P<0.001). These changes were prevented by administration of triiodothyronine or insulin. Ventricular fibrillation during reperfusion was abolished in hearts from diabetic rats. This protection was prevented by treatment with either triiodothyronine or insulin. Hearts from methimazole-hypothyroid rats also showed no ventricular fibrillation during reperfusion. The protection against ischaemia-reperfusion-arrhythmias observed in hearts from streptozotocin-diabetic rats may be due to diabetes-induced hypothyroidism.

Topics: Animals; Arrhythmias, Cardiac; Blood Glucose; Body Temperature; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Heart; Heart Rate; Hypothyroidism; Insulin; Long QT Syndrome; Male; Methimazole; Myocardial Ischemia; Myocardial Reperfusion Injury; Organ Size; Protein Kinase C; Rats; Rats, Sprague-Dawley; Streptozocin; Thyroid Hormones; Triiodothyronine; Ventricular Fibrillation

A specific phenotype of methimazole (MMI) induced malformations has recently been postulated. MMI embryopathy is characterized by minor dysmorphic features, choanal atresia and/or esophageal atresia, growth retardation, and developmental delay.. We prospectively studied the outcome of pregnancy in 241 women counseled by 10 Teratology Information Services (TIS) of the European Network of Teratology Information Services (ENTIS) because of MMI exposure, and compared them with those of 1,089 pregnant women referred to TIS because of exposure to nonteratogenic drugs (control group). Information was obtained by mail or telephone interview.. There was no increase in the general rate of major anomalies or of spontaneous or induced abortions in the MMI-exposed group in comparison with the control group. Two newborns were affected with one of the major malformations that are part of the postulated embryopathy.. The results of this study indicate that choanal as well as esophageal atresia may have a higher incidence than expected in fetuses exposed to MMI between 3 and 7 gestational weeks. Until further data are available, thyrotoxicosis should be treated with propylthiouracil, as it is apparently safer for use during the fertile period.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Age Factors; Body Weight; Cohort Studies; Developmental Disabilities; Esophageal Atresia; Europe; Female; Humans; Infant, Newborn; Information Services; Male; Methimazole; Phenotype; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Teratogens; Time Factors

In order to ascertain whether methimazole, a drug commonly used for the treatment of hyperthyroidism, interferes with the progression of autoimmune-mediated myocardial injury, we investigated the effect of methimazole on experimental autoimmune myocarditis (EAM) in rats. EAM was induced by immunization with porcine cardiac myosin. Methimazole administration markedly slowed the body weight growth in both normal and EAM rats, but did not induce morphologic change of cardiac tissue in normal rats. In EAM rats, macroscopic examination revealed discoloration of the cardiac surface, and histopathological examination by light microscopy showed extensive myocardial necrosis, infiltration by inflammatory cells and myocardial fibrosis. In the EAM rats treated with methimazole, the discolored areas on the cardiac surface were markedly diminished in size, and the myocardial necrosis, cellular infiltration and fibrosis were significantly less severe. To identify the mechanism responsible of this effect, we investigated the change of regulatory lymphocyte subsets in peripheral blood using an immunofluorescence technique with a flow cytometer. A decrease in the helper/suppressor T cell ratio as a result of the increased proportion of suppressor T cells and a decrease in the proportion of B cells were observed in normal rats after methimazole administration, and similar findings were made in the EAM rats treated with methimazole. These results indicate that methimazole interferes with the progression of EAM, and immunosuppression may, at least in part, be involved in the inhibitory effect of methimazole on EAM in rats.

Topics: Animals; Autoimmune Diseases; Body Weight; CD4-CD8 Ratio; Immunosuppressive Agents; Male; Methimazole; Myocarditis; Myocardium; Organ Size; Rats; Rats, Inbred F344

The effect of the antithyroid drug methimazole (MMI) on cytochrome P450/P450 reductase-dependent activation of the anti-cancer prodrug cyclophosphamide (CPA) was investigated in a rat model of P450 prodrug activation-based cancer gene therapy. MMI treatment decreased the expression of hepatic P450 reductase by approximately 75% but did not alter P450 reductase levels in a 9L gliosarcoma growing in vivo as a subcutaneous solid tumor. In a pharmacokinetic study, MMI treatment significantly decreased the peak plasma concentration of the active, P450-generated metabolite 4-hydroxy-CPA, from 84.1 to 57.8 microM, and substantially prolonged its apparent half-life, from 25.4 to 54.3 minutes. The area under the plasma concentration x time curve and clearance values for 4-hydroxy-CPA were largely unchanged, however, indicating that MMI decreases the rate but not the overall extent of hepatic CPA activation. MMI alleviated some of the systemic toxicities of CPA treatment, as judged by the moderation of CPA-induced body weight loss and hematuria. The impact of MMI on CPA antitumoral activity was evaluated in rats implanted with 9L tumors transduced with P450 reductase in combination with the CPA-activating P450 2B1, which confers the capacity for intratumoral prodrug activation and leads to markedly enhanced chemosensitivity. CPA given as a single, subtherapeutic dose of 75 mg/kg resulted in a 13.8 day growth delay, whereas CPA in combination with MMI increased the growth delay to 17.4 days. By contrast, a tumor growth delay of only 3.4 days was observed in animals bearing 9L wild-type tumors given the same drug combination. We conclude that the selective reduction of liver P450 reductase after MMI treatment decreases the rate of hepatic drug activation and the host toxicity of CPA without loss of the antitumoral effect, thus increasing the therapeutic index of CPA in a P450-based cancer gene therapy model, where CPA undergoes localized drug activation at its intratumoral site of action.

Topics: Animals; Antineoplastic Agents, Alkylating; Area Under Curve; Body Weight; Cell Division; Cyclophosphamide; Dose-Response Relationship, Drug; Enzyme Activation; Genetic Therapy; Gliosarcoma; Half-Life; Liver; Male; Methimazole; NADPH-Ferrihemoprotein Reductase; Prodrugs; Rats; Rats, Inbred F344; Skin Neoplasms; Tumor Cells, Cultured

Adults rats with hypothyroidism were prepared by administration of 6-propyl-2-thiouracil (PTU) or methimazole, and the tissues were examined for their gangliosides through methods including glycolipid-overlay techniques. Normal thyroid tissue contained GM3, GD3, and GD1a as the major gangliosides, with GM1, GD1b, GT1b, and GQ1b in lesser amounts. The goitrous tissue of PTU-induced hypothyroid rats had higher concentrations of GM1 and GD1a with a concomitant decrease of GM3. The amount of GT3 in thyroid tissue was increased in hypothyroid animals. While normal liver tissue had a complex ganglioside pattern with a- and b-series gangliosides, the PTU-induced hypothyroid tissue showed a simpler ganglioside profile that consisted mainly of a-series gangliosides with almost undetectable amounts of b-series gangliosides. The expression of c-series gangliosides was suppressed in the hypothyroid liver tissue. Heart tissue had higher contents of GM3 and GT3 than control. No apparent change was observed in the compositions of major and c-series gangliosides in other extraneural tissues (i.e., kidney, lung, spleen, thymus, pancreas, testis, skeletal muscle, and eye lenses), and neural tissues (i.e., cerebrum and cerebellum) from PTU-induced hypothyroid rats. The ganglioside changes of thyroid, liver, and heart tissues were reproduced in corresponding tissues of methimazole-induced hypothyroid rats. These results suggest that hypothyroid conditions affect the biosynthesis and expression of gangliosides in specific tissue and cell types.

Topics: Animals; Body Weight; Gangliosides; Heart; Hypothyroidism; Liver; Male; Methimazole; Myocardium; Propylthiouracil; Rats; Rats, Sprague-Dawley; Reference Values; Thyroid Gland; Thyroxine

This study examined the effects of polychlorinated biphenyls (PCBs) on development of families of amphibians using the African clawed frog (Xenopus laevis) and the European common frog (Rana temporaria). Amphibians were orally exposed to the technical PCB-mixture Clophen A50 or to the non-ortho-3,3',4,4',5-CB congener (PCB 126) either for a 10-day period or until metamorphosis. Occurrence and rate of malformations, mortality, period until metamorphosis and thyroid hormone levels were measured. Mortality increased in a dose-dependent manner, as did the rates of malformation. Time until metamorphic transformation was prolonged and the weight of froglets was increased. Although not statistically significant, thyroid hormone levels were also lowered. PHAHs such as PCBs may affect important aspects of amphibian fitness and may influence amphibian reproductive success.

Topics: Administration, Oral; Animals; Antithyroid Agents; Body Weight; Environmental Pollutants; Imidazoles; Larva; Metamorphosis, Biological; Mortality; Polychlorinated Biphenyls; Rana temporaria; Thyroid Hormones; Xenopus laevis

The purpose of these studies was to determine the effect of thyroidectomy (Tx), and thyroid hormone (T3/T4) treatment on concentrations of plasma CT in chicks. In addition, the turnover of CT in Tx- and T3/T4-treated chicks was estimated using a novel nonradioactive salmon CT preparation. One-week-old broiler chicks (Gallus domesticus) (n = 75) were divided into three groups. Group I was sham-injected daily (i.m. saline), Group II was injected with 50 micrograms/day of T3/T4 while Group III was injected with the goitrogen, methimazole, (150 mg/kg BW per day) for 8 weeks. Chicks (8-9 weeks old) were implanted with catheters in the brachial wing vein and administered ruthenium-labeled salmon CT. Blood samples were collected at 30 s, 1, 2, 4, 8, 20 min, and 3 h after injection. Results showed that concentrations of plasma CT were decreased in T3/T4-injected birds. There was no significant effect of methimazole on circulating concentrations of plasma CT. The half-life of CT was significantly increased (P < 0.05) in both T3/T4-injected (n = 6; 1.34 +/- 0.16 min) and goitrogen-treated birds (n = 2; 5.81 +/- 2.83 min) compared to controls (n = 7; 54 +/- 3 s) The results demonstrate that changes in concentrations of plasma thyroid hormones can significantly affect concentrations of plasma CT.

Topics: Aging; Animals; Antithyroid Agents; Body Weight; Calcitonin; Calcium; Chickens; Female; Methimazole; Organ Size; Thyroid Gland; Thyroidectomy; Thyroxine; Triiodothyronine

A three-part study explored the basis for an interaction between changes in thyroid status and bulbospinal serotonin (5HT) metabolism. In experiment 1, three well-characterized models of primary hypothyroidism were all accompanied by significant increases in 5HT metabolism. In experiment 2, circulating thyroid hormone levels were experimentally varied from very low methimazole (Meth) treatment to very high (T3 implants: 2.5, 5.0, or 7.5 mg triiodothyronine). As in experiment 1, Meth led to elevated 5HT. Hyperthyroidism was accompanied by significant reductions in 5HT, while urinary norepinephrine excretion paralleled 5HT. In experiment 3, rats were subjected to Meth either 2 weeks before or after induction of diabetes with streptozotocin (Stz). Meth prevented Stz-associated reductions in 5HT and attenuated development of hyperphagia. Meth could not reverse established Stz-associated reduction in 5HT or hyperphagia, although both were slightly attenuated. Thus, although the first two experiments argue for a simple inverse relationship between circulating thyroid hormone levels and 5HT in the brain, experiment 3 demonstrated that Stz-associated decrements in 5HT could not be reversed by subsequent lowering of circulating thyroid hormone. Nor did accompanying measurements indicate that glycemic status or circulating levels of leptin were important predictors of 5HT. Thus the interaction between thyroid hormones and 5HT is both more subtle and more complex than previously thought.

Topics: Animals; Blood Glucose; Body Weight; Brain Stem; Diabetes Mellitus, Experimental; Hydroxyindoleacetic Acid; Hyperphagia; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Norepinephrine; Rats; Rats, Sprague-Dawley; Serotonin; Spinal Cord; Thyroid Hormones; Tryptophan

This study was designed to examine the role of flavin-containing monooxygenase (FMO) on the auditory and vestibular neurotoxicity of 3,3'-iminodipropionitrile (IDPN) using the FMO substrate and competitive inhibitor methimazole (MMI). Specifically, the purpose was to block the FMO-mediated conversion of IDPN to the putative neurotoxic metabolite N-hydroxy3,3'-iminodipropionitrile (HOIDPN). In three separate experiments, adult male Long-Evans hooded rats were administered (ip) saline (vehicle), MMI, IDPN, or HOIDPN individually, or a combination of IDPN and MMI or HOIDPN and MMI. Animals were observed daily for signs of the ECC syndrome (excitation with choreiform and circling movements) for 10 days. One to 2 weeks after exposure, a battery of behavioral tests was used to examine vestibular and auditory function. MMI completely blocked the neurotoxicity associated with a 600 mg/kg dose of IDPN and partially blocked the effects of a 1000 mg/kg dose of IDPN. In contrast, MMI failed to block, and instead increased, the neurotoxicity associated with HOIDPN. These data suggest that FMO-mediated metabolism of IDPN is necessary for the generation of a metabolite responsible for the vestibular and auditory neurotoxicities.

Topics: Animals; Behavior, Animal; Body Weight; Enzyme Inhibitors; Hearing; Male; Methimazole; Motor Activity; Neurotoxins; Nitriles; Oxygenases; Rats; Vestibular Function Tests; Vestibular Nerve; Vestibule, Labyrinth; Vestibulocochlear Nerve

A 56-year-old female with Graves' disease who presented with decreased secretion of gonadotropins is described. She was admitted to hospital because of her being in a state of confusion. One month before admission she had been diagnosed as having Graves' disease and was treated with methimazole since then. Plasma LH and FSH levels were undetectable, and their responses to LH-RH were extremely decreased in spite of undetectable levels of plasma estradiol and estriol. One year after treatment, both basal and stimulated values of LH and FSH reverted to normal as did those of TSH. Reversible suppression of gonadotropins as described herein has never been reported in cases of Graves' disease.

Topics: Antithyroid Agents; Body Weight; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Graves Disease; Humans; Luteinizing Hormone; Methimazole; Middle Aged; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine

The aim of this study was to assess the impact on neonatal neurobehavioral development of methimazole (MMI)-induced in-utero hypothyroxinemia and of correction by maternal-fetal thyroxine (T4) transfer in the rat. Two groups of pregnant Sprague-Dawley rats received MMI as drinking water from gestation day 10 until birth. From day 16 until parturition, one of these groups received daily intraperitoneal injections of L-T4 and the other received saline injections. A third (control) group drank tap water and received saline injections. From day of birth, offspring from all groups were raised by untreated foster dams. Their neurobehavioral development was monitored, on postnatal days 5-14 (N = 3/litter, from 30 litters) by experimenters blind to treatment group. Prenatal T4 treatment resulted in correction of MMI-induced delayed appearance of three different reflexes. Body-weight gain of treated pups was similar to that of controls and more rapid than development of rats treated with MMI-alone. T4 treatment did not prevent, however, MMI-induced delay in maturation of physiological landmarks (e.g. ear opening). At least a portion of the developmental delay resulting from prenatal (maternal) MMI administration may be reversed by maternal-fetal transfer of T4 administered to the gravid dam.

Topics: Administration, Oral; Animals; Animals, Newborn; Antithyroid Agents; Behavior, Animal; Body Weight; Embryonic and Fetal Development; Female; Hypothyroidism; Male; Methimazole; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Thyroxine

This paper describes the effects of goitrogen-induced hypothyroidism on GH, prolactin and the testis size of rats. Hypothyroidism was caused by lifetime-rearing on goitrogen methimazole (MMI). This condition was brought on by adding 0.025% (Weight/ Volume) MMI to the mother's drinking water immediately after birth. Offspring, after weaning, were given the same food and drinking water as that of the mother until sacrified. Four experimental groups were designed: group 1, CMF (normal rat chow) and tap water; group 2, CMF with 0.025% thyroid powder and tap water; group 3, CMF and tap water containing 0.025% MMI and group 4, CMF with the thyroid powder and tap water containing 0.025% MMI. The rats were killed at 73 days of age after rearing under the 4 conditions described. Pituitary GH and PRL and serum PRL were significantly less in group 3 than in the others. Testis weight was the same for groups 3 (2.51 +/- 0.14 g; Mean +/- SD), 1 (2.76 +/- 0.07 g) and 2 (2.60 +/- 0.06 g). Increased testis weight was noted only in group 4 (3.25 +/- 0.1 g). The ratio of testis to body weight was significantly higher in group 3 than in the other groups. The authors concluded that hypothyroidism causes pituitary dysfunction with GH and PRL deficiency and also causes testis enlargement with age.

Topics: Animals; Antithyroid Agents; Body Weight; Female; Growth Hormone; Hypertrophy; Hypothyroidism; Male; Methimazole; Organ Size; Pituitary Gland; Pregnancy; Prolactin; Rats; Rats, Wistar; Testis; Thyrotropin; Thyroxine

This study examined the effect of ambient temperature on perirenal adipose tissue development and thermoregulation over the first month of postnatal life in lambs treated with a drug that reduces thyroid hormone synthesis (methimazole; at a dose of 50 mg day-1 (kg body weight)-1). Twin lambs were hand-reared at a fixed level of nutrition in either a warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperature. Oxygen consumption, heart rate and colonic temperature were measured during non-rapid eye movement sleep in different ambient temperatures (6, 15, 25 and 34-36 degrees C) at 7, 14 and 28 days of age. Plasma thyroid hormone concentrations decreased with postnatal age and were higher in CR than in WR lambs. All lambs increased plasma thyroid hormone concentrations and O2 consumption during cold exposure but this was associated with a mean increase in colonic temperature in WR lambs at 7 or 28 days. Colonic temperature increased with the onset of panting at all ages when lambs were exposed to 34-36 degrees C, a response that was greatest at 28 days in CR lambs. An increase in colonic temperature with age was observed in CR but not WR lambs. Heart rate declined with age only in the WR group. At 8 and 29 days there were no significant differences between WR and CR groups in the occurrence of shivering or in the thermogenic activity (i.e. GDP binding to mitochondria) of perirenal adipose tissue. At 29 days WR lambs possessed more adipose tissue with a higher lipid and DNA content. It is concluded that modest changes in rearing temperature can have a large influence on the control of body temperature and thyroid hormone response to methimazole treatment. CR lambs are able to maintain higher plasma thyroid hormone concentrations and exhibit improved thermoregulation compared with WR lambs without any detectable differences in brown adipose tissue function.

Topics: Adipose Tissue; Animals; Animals, Newborn; Antithyroid Agents; Body Temperature Regulation; Body Weight; Methimazole; Sheep; Sleep, REM; Temperature; Thyroid Hormones

We have recently reported that hypothyroidism increases immunoreactive (IR)-vasoactive intestinal polypeptide (VIP) and VIP mRNA content in both parvocellular and magnocellular neurons of the rat, hypothalamic paraventricular nucleus (PVN). As VIP can stimulate vasopressin (AVP) secretion, we conducted an anatomical investigation to determine whether VIP-containing neurons in other regions of the brain that are involved with homeostatic mechanisms of water and salt conservation are also affected by hypothyroidism. The distribution and intensity of VIP immunostaining in neurons and fibers of the magnocellular-neurohypophysial system, including the hypothalamic PVN, supraoptic nucleus (SON) and accessory magnocellular cell groups, circumventricular subfornical organ (SFO), preoptic and anterior hypothalamus, midline thalamus, subthalamic zona incerta and posterior septal nuclei were studied using a highly sensitive immunocytochemical technique and unbiased neuronal counting methods, based on the optical dissector principle. Hypothyroidism increased the intensity of VIP immunostaining and/or the number/section, percentage and numerical density of IR-VIP neurons in the PVN, SON, nucleus circularis, periventricular preoptic nucleus of the hypothalamus and SFO. In addition, IR-VIP perikarya and/or fibers in the hypothalamic medial preoptic area and anterior periventricular nucleus, nucleus reuniens of the thalamus and dorsal fornix-triangular septal nucleus complex were also apparent in the hypothyroid animals while no immunostaining was seen in these areas in control animals. No quantitative and/or qualitative modifications in IR-VIP neurons and fibers were noted in the anterior hypothalamic area, suprachiasmatic nucleus, thalamic paraventricular nucles an subthalamic zona incerta between hypothyroid and control animals. These findings suggest an inverse relationship between thyroid hormone and VIP content and/or distribution of IR-VIP neurons in specific forebrain regions involved in the control of AVP release, extracellular fluid volume, thirst, blood pressure and anterior pituitary secretion. This raises the possibility that changes in fluid homeostasis and cardiovascular function occurring in hypothyroidism may be mediated, at least in part, by VIP-producing neurons in diverse regions of the brain.

Topics: Animals; Antithyroid Agents; Body Weight; Hypothyroidism; Immunohistochemistry; Male; Methimazole; Nerve Fibers; Neurons; Pituitary Gland, Posterior; Prosencephalon; Rats; Rats, Sprague-Dawley; Thyroid Hormones; Vasoactive Intestinal Peptide

A 90-day gavage study was performed to evaluate the subchronic toxicity of 1-methyl-3-propylimidazole-2-thione (PTI) when administered to Crl:CD BR rats. PTI is a chemical catalyst and is structurally similar to the thioureas, which are known to adversely affect the thyroid. Therefore, this study was designed to investigate the effects of PTI on the thyroid. Male and female rats were dosed with 0, 5, 10, 25, or 75 mgPTI/kg/day for 13 weeks. Clinical pathology examinations and pathology examination were performed and the following were measured periodically: serum T3, T4, and TSH, hepatic UDP-glucuronyltransferase activity, and cell proliferation of the thyroid and liver. Under the conditions of this study, the overall no-observed-adverse-effect level (NOAEL) for the subchronic effects of PTI in male and female rats was 10 mg PTI/kg/day. The NOAEL was based on the effects on the thyroid gland in male and female rats dosed with 25 and 75 mg PTI/kg/day, as well as the hepatic centrilobular fatty change, increased severity of chronic progressive nephropathy, fatty change in the adrenal medulla, and the substantial reduction in body weight and body weight gain. The primary target organs were the thyroid and liver. Alterations in thyroid hormones (T3, T4, and TSH) occurred predominantly at 25 and 75 mg/kg/day. Toxicologically significant alterations in T3, T4, and TSH levels, cell proliferation, and UDP-glucuronyltransferase activity occurred in rats dosed with 25 and 75 mg/kg/day, which correlated with organ weight and histopathological effects. Additionally, the effect of PTI on thyroid peroxidase activity, a key step in thyroid hormone synthesis, was evaluated in vitro using microswine thyroid microsomes. PTI was shown to inhibit thyroid peroxidase, with an IC50 of 0.02 M. These data suggest that PTI enhances the excretion of T4 via induction of glucuronyltransferase and inhibits thyroid hormone synthesis via a direct affect on thyroid peroxidase. Both of these effects contribute to the disruption of the hypothalamic-pituitary-thyroid axis and result in sustained elevation of TSH and the corresponding thyroid hypertrophy and hyperplasia.

Topics: Animals; Body Weight; Cell Division; Eating; Female; Glucuronosyltransferase; In Vitro Techniques; Intubation, Gastrointestinal; Iodide Peroxidase; Liver; Male; Methimazole; Organ Size; Rats; Swine; Swine, Miniature; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

The thymus, as part of the immune-neuroendocrine axis, is greatly influenced by factors from most endocrine glands, especially the thyroid. Antithyroid drugs (carbimazole and methimazole) were used to induce hypothyroidism in rats. Histological and ultrastructural examination of the thymus showed progressive thymic involution after 4 weeks of drug treatment to the end of observations (7 weeks). The involution was characterised by increased thymocyte apoptosis and thymocyte phagocytosis by macrophages. This resulted in thymocyte depopulation, increases in numbers of interdigitating cells, alterations to mainly subcapsular and medullary epithelial cells, an apparent increase of mast cells and collagen in the capsule and septa, and increased numbers of B cells and plasma cells. Lymphoid cells immuno-reactive with MRC OX12 (which detects B cells) were observed within blood vessel walls, suggesting that they may have been moving in and out of the thymus. The administration of drugs causing hypothyroidism, therefore, also caused marked involution of the thymus.

Topics: Animals; Apoptosis; Body Weight; Carbimazole; Epithelium; Hypothyroidism; Immunohistochemistry; Macrophages; Male; Methimazole; Organ Size; Rats; Rats, Wistar; Thymus Gland; Triiodothyronine

The aim of the present study was to investigate the influence of thyroid hormones on androgen metabolism in Sertoli cells isolated from 3- and 4- week-old rats. Hypothyroidism was induced by the oral administration of 0.025% methimazole (MMI) from birth until the rats were killed at 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with L-triiodothyronine (T3 3 micrograms/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Indeed, body and testicular weights were similar in 4-week-old hypothyroid animals to those in 3-week-old control rats. Testosterone metabolism in Sertoli cells isolated from 3- and 4-week-old hypothyroid rats was mainly expressed by the lowering of 5 alpha-dihydrotestosterone + androstane 3 alpha, 17 beta-diol and an enhanced formation of 5 alpha-reduced steroids with poor androgenic properties (e.g. 5 alpha-androstane, 3, 17 alpha-dione (androstanedione), 5 alpha-androstane, 3-ol-17-one (androsterone)). Treatment of the same group of animals with T3 in vivo and in vitro did not influence the pattern of 5 alpha-reductase steroids substantially. The most striking finding in the Sertoli cells of 3-week-old hypothyroid rats was the dramatic enhancement of oestradiol formation which persisted to a lesser extent 1 week later.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Androgens; Androstane-3,17-diol; Androstenedione; Androsterone; Animals; Body Weight; Cells, Cultured; Dihydrotestosterone; Estradiol; Hypothyroidism; Male; Methimazole; Organ Size; Rats; Rats, Wistar; Sertoli Cells; Sexual Maturation; Testis; Testosterone; Triiodothyronine

The purpose of this work was to study if TSH has a role in TPO antigen expression in vivo. Using the cytotoxicity assay we measured TPO expression and correlated it with TSH serum levels in 3 groups of rats: control, hypothyroid and hypothyroid supplemented with thyroxine. For comparative purposes, in the cytotoxicity assay we used rat monoclonal antiTPO or human sera with high titles for antiTPO antibodies. Hypothyroid rats showed marked elevations of TSH serum levels and TPO antigen expression in their thyrocytes when compared to the control and supplemented group. A positive correlation between TPO antigen and TSH levels was observed (r = 0.69, p < 0.001). There was an excellent correlation between TPO results using rat monoclonal or human sera antibodies (r = 0.94 p < 0.0001). It is concluded that TSH modulates TPO antigen expression. These data are of clinical relevance considering that TSH modulates the expression of other antigens that can maintain the immune response and perpetuate the immune disease in patients with Graves disease treated with antithyroid drugs. Thus, the avoidance of TSH hypersecretion with administration of thyroxine could be useful to treat these patients.

Topics: Analysis of Variance; Animals; Body Weight; Humans; Hypothyroidism; Iodide Peroxidase; Male; Methimazole; Rats; Rats, Sprague-Dawley; Thyrotropin; Thyroxine; Time Factors

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Binding, Competitive; Blood Pressure; Body Weight; Cerebral Cortex; Endothelins; Heart Rate; Hyperthyroidism; Hypothalamus; Hypothyroidism; Iodine Radioisotopes; Kinetics; Male; Methimazole; Pituitary Gland; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Thyroxine; Triiodothyronine

We showed previously that thyroid antagonists and glucocorticoids partially alleviated the impaired righting ability and abnormally high levels of plasma creatine kinase activity in genetically dystrophic chicks. The goals of the present study were: (1) to ascertain whether the beneficial effects of methimazole (MMI; thyroid antagonist) on muscle function and plasma creatine kinase (CK) activity in dystrophic chickens are correlated with significant reduction in plasma triiodothyronine (T3) and thyroxine (T4); (2) to assess whether the MMI-induced thyroid changes are accompanied by increased plasma corticosterone level and/or changes in muscle glucocorticoid receptors which might account partially for the beneficial effects of MMI; and (3) to determine if plasma T3 and T4 are reduced in dexamethasone (DEX) treated dystrophic chickens which might account at least partially for the beneficial effects of DEX (a potent glucocorticoid) on avian dystrophy. The data show that beneficial effects of MMI are associated with reduced plasma levels of thyroid hormones and increased circulating levels of corticosterone. In addition, DEX actually increases plasma T3 levels. These differential effects indicate that reduced plasma thyroid hormone levels do not represent a common mechanism of beneficial drug effects in avian muscular dystrophy. On the other hand, elevated plasma glucocorticoid levels accompany the beneficial effects of both severe hypothyroidism and DEX treatment. The data also show that MMI induces down-regulation of muscle cytosolic glucocorticoid receptors which are higher than normal in dystrophic muscles.

Topics: Animals; Body Weight; Chickens; Corticosterone; Creatine Kinase; Dexamethasone; Male; Methimazole; Muscles; Muscular Dystrophy, Animal; Receptors, Glucocorticoid; Thyroid Gland; Thyroxine; Triiodothyronine

In the central nervous system, type II 5' deiodinase (5'D-II) is highly regulated, as judged by the dramatic changes in enzyme levels observed after abrupt alterations in thyroid status. In this work, the 5'-DII activity has been studied in different situations of experimental hypothyroidism (propylthiouracil, methimazole, thyroidectomy, and low iodine diet), in various brain regions (pituitary, cerebellum, brain stem, hypothalamus, cortex, and whole brain) in adult rats. Propylthiouracil and methimazole significantly increase the activity in all brain regions. These increases are higher in rats treated with methimazole. Thyroidectomy significantly increases the activity in cortex and pituitary. A low iodine diet significantly increases in all brain regions except in the hypothalamus. The concentration of triiodothyronine (T3) studied in the major brain regions remained unchanged. The results obtained show a compensatory mechanism in pituitary and other brain regions in order to maintain the T3 levels in brain tissue.

Topics: Animals; Body Weight; Brain; Cytosol; Diet; Dithiothreitol; Glycerolphosphate Dehydrogenase; Hypothyroidism; Iodide Peroxidase; Liver; Malate Dehydrogenase; Male; Methimazole; Mitochondria, Liver; Propylthiouracil; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthryoid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 +/- 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. No ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyrodism after NA ipodate was discontinued, and she was then treated with MMI. MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Body Weight; Female; Graves Disease; Heart Rate; Humans; Ipodate; Male; Methimazole; Prospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Treatment of male rat pups with the reversible goitrogen 6-propyl-2-thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth to day 25, increases their testis size and daily sperm production (DSP) at 160 days of age by up to 80% and 140%, respectively. The purpose of this study was to examine the effectiveness of various concentrations of PTU and determine the PTU dose that would maximize testis growth while minimizing side effects such as decreased maternal water consumption and decreased pup growth. Whether this effect was specific to PTU was determined by evaluating the effects of another commonly used goitrogen, methimazole (MMI), in increasing adult testis size and sperm production. Dams were given PTU (0.1-0.0004% w/v) or 0.025% MMI (w/v) in their water from birth to day 25 post partum, then given no further treatment. Thyroxine concentrations were measured in all groups of pups at 25, 35 and 45 days, and testis weight and DSP were determined at 90 days of age. At 25 days of age, thyroxine concentrations were maximally decreased by PTU treatments of 0.0015% or greater; less severe decreases were produced by 0.0004% PTU or 0.025% MMI. Thyroxine concentrations increased in all treated groups at day 35 compared with day 25, and returned to normal by day 45. At 90 days of age, testis weight was increased by about 40% in rats whose mothers had been treated with doses of 0.006% PTU or greater, whereas testis weights in groups given 0.0015 and 0.0004% PTU or 0.025% MMI were increased 31, 15 and 18%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Body Weight; Dose-Response Relationship, Drug; Drinking; Drug Administration Schedule; Embryonic and Fetal Development; Male; Methimazole; Organ Size; Propylthiouracil; Rats; Rats, Sprague-Dawley; Spermatogenesis; Testis; Thyroxine

Thyroid hormone is essential for normal growth and development. For certain T4 effects, there is a critical period during ontogeny when normal T4 levels are required, and thyroid replacement after that period cannot correct the changes in hypothyroid animals. We have previously described a prolonged high expression of serum insulin-like growth factor binding protein (IGFBP)-2 during the perinatal period in congenitally hypothyroid rats. To see if this effect was confined only to a certain period during rat ontogeny, we made rats hypothyroid with methimazole treatment either prenatally, or at different postnatal ages from 1 to 14 days of life, and at adult age. Serum IGF-I levels were reduced by approximately 30% in all the 18-day-old hypothyroid animals, and did not correlate with the duration of the hypothyroid state. Serum IGF-I levels in the adult animals were 50% of control levels. At the age of 18 days, control animals had only very low levels of IGFBP-2 demonstrable by western ligand blotting, whereas the congenitally hypothyroid animals had elevated levels. Pups placed on methimazole treatment since the first day of life showed higher IGFBP-2 levels at the age of 18 days, although the change was not as prominent as in the congenitally hypothyroid animals (200% vs. 500% of control levels, respectively). Binding protein changes were approximately 2-fold at the mRNA level. Rats started on methimazole after the first 5 days of life showed normal low levels of IGFBP-2 at the age of 18 days. Abnormal IGBFP-2 expression in congenitally or neonatally hypothyroid animals could be corrected by thyroid hormone replacement, if started during the first week of the life, but not later. In adult hypothyroid animals, there was no induction of IGFBP-2 expression, but the levels of IGFBP-3 and -4 were decreased to 80% and to 30% of control levels, respectively. IGFBP-3 messenger RNA (mRNA) levels were decreased to 50% of control levels but IGFBP-4 mRNA levels were paradoxically increased in the hypothyroid animals. All these changes could be corrected by T4 replacement. In conclusion, there exists a critical period during the perinatal development of the rat, when thyroid hormone is essential for a subsequent normal IGFBP-2 ontogenic pattern. Adult animals show a completely different IGFBP response to hypothyroidism, with a decrease of IGFBP-3 and -4 levels. Thus, the effects of thyroid hormone on IGF-IGFBP axis regulation depend on the developmental stage of the an

Topics: Aging; Animals; Animals, Newborn; Body Weight; Carrier Proteins; Female; Gene Expression; Hypothyroidism; Insulin-Like Growth Factor Binding Protein 2; Male; Maternal-Fetal Exchange; Methimazole; Milk; Pregnancy; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger; Somatomedins; Thyrotropin; Thyroxine

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Topics: Animals; Blood Pressure; Body Weight; Cardiomegaly; Hypertension; Kidney; Male; Methimazole; Rats; Rats, Inbred Strains; Renin

Resting oxygen consumption (VO2) and mitochondrial GDP binding were measured in hypothyroid and euthyroid rats after administration of selective and nonselective beta-adrenoceptor agonists (BRL 35135A and Isoprenaline--BRL, ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-agonists were lower in hypothyroid rats than in the euthyroid group. The reduced response was more marked for ISO than for BRL. These results suggest that BRL is acting on a beta-adrenoceptor which differs from beta-1 and beta-2 adrenoceptors, responsible for the effect of ISO. Activation of thermogenesis via this beta-3 adrenoceptor seems to be less dependent on permissive levels of thyroid hormones than on activation via beta-1 and/or beta-2 adrenoceptors.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Animals; Body Weight; Disease Models, Animal; Guanosine Diphosphate; Hypothyroidism; Isoproterenol; Male; Methimazole; Oxygen Consumption; Phenethylamines; Rats; Rats, Sprague-Dawley; Thermoreceptors; Thyroidectomy

The effects of thyroid status on the binding capacity, association constant (Ka) and receptor occupancy during postnatal rat testis development were evaluated. Hypothyroidism (induced by oral administration of 0.05% methimazole from the day of birth) increased the total T3 binding capacity in the testis, retarding the normal developmental decrease in T3 receptor number (mean maximal binding capacities estimated by Scatchard analysis for 21-day-old eu- and hypothyroid rats were 117 and 173 fmol/mg DNA, respectively). The rat thyroid status also affected the percentage of T3 receptor occupancy but not the affinity of binding (as measured by Ka). The postnatal developmental changes in T3 binding capacity induced by hypothyroidism were completely reversed by T3 replacement. These results suggest that T3 nuclear receptors in the developing rat testis are modulated by thyroid hormones.

Topics: Animals; Body Weight; Cell Nucleus; Hypothyroidism; Male; Methimazole; Rats; Rats, Inbred Strains; Receptors, Thyroid Hormone; Sertoli Cells; Testis; Thyroid Hormones; Triiodothyronine; Up-Regulation

Treatment of mice with methimazole was found to modulate diabetes development following low-dose (5 x 40 mg/kg body weight) streptozotocin administration. The administration of 0.2 or 1 mg methimazole per kg body weight for 1-3 weeks significantly enhanced hyperglycemia. The enhancing effect of methimazole was also seen when administration began only after termination of streptozotocin injections. Methimazole treatment did not potentiate diabetes induced by a single high dose of streptozotocin (175 mg/kg). Serum thyroxin levels were not affected due to the short period of thyrostatic treatment. Semiquantitative immunocytochemistry of inflamed islets did not show a stronger influx of immune cells but rather a high activation state of infiltrated macrophages (M1/70 positive). We conclude that methimazole enhances the development of immune-mediated diabetes.

Topics: Animals; Antibodies, Monoclonal; Body Weight; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Drug Synergism; Immunohistochemistry; Islets of Langerhans; Macrophages; Male; Methimazole; Mice; Mice, Inbred C57BL; Streptozocin; Thyroxine

Noxythiolin (Noxyflex-S) inhibited iodide organification (thyroid hormone synthesis) by cultured porcine thyrocytes in vitro after 5 hr (IC50 approx. 9.0 microM). The positive control, the anti-thyroid thiourea methimazole, was about 15 times more potent an inhibitor of iodide organification (IC50 approx. 0.6 microM) under the same incubation conditions. In an in vivo assessment of follicular organification capacity using the perchlorate discharge test, 14 days of ip treatment of male Charles River rats with noxythiolin (50 mg/kg body weight) produced no inhibition of iodide organification when tested 24 hr after the last administration of noxythiolin whereas the positive control, propylthiouracil, was a highly potent inhibitor.

Topics: Animals; Body Weight; Cells, Cultured; Injections, Intraperitoneal; Iodine; Male; Methimazole; Noxythiolin; Organ Size; Propylthiouracil; Rats; Swine; Thyroid Gland; Thyroid Hormones

Ten hyperthyroid patients were assessed for muscle strength before and after a period of medical treatment that averaged 12 months. The subjects did not change their habitual level of physical activity between the two test occasions. Maximal voluntary isokinetic knee extensor muscle strength was determined during various concentric, eccentric and isometric conditions. Average increases in strength from before to termination of treatment ranged from 25 to 41% for the concentric and isometric tests (P less than 0.01, n = 10), and from 19 to 35% for the eccentric tests (P less than 0.01, n = 6). The present study demonstrates that medical treatment of hyperthyroid patients results in a marked increase in muscle strength.

Topics: Adult; Analysis of Variance; Body Weight; Female; Humans; Hyperthyroidism; Male; Methimazole; Muscles; Propranolol; Thiouracil

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Guanosine Diphosphate; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Mitochondria; Organ Size; Oxygen Consumption; Rats; Rats, Inbred Strains; Reference Values; Thyroid Gland

The influence of hypothyroidism on testicular steroidogenesis was investigated by evaluating the production of testosterone and its precursors by isolated testes from adult male rats. Animals were made hypothyroid starting from the 4th week of life either by daily oral administration of 0.1% methimazole (MMI) or by surgical thyroidectomy (TZ). Half of the thyroidectomized rats were i.p. injected with 3 gamma T3/100 g body weight on alternate days during the last three weeks before sacrifice. Hypothyroidism is associated with a severe retardation of body growth, which appears more marked in thyroidectomized than in MMI treated rats; no significant variations in testis weight are observed. Administration of T3 does not completely restore body weight. A significant decrease in the "in vitro" production of testosterone and its precursors by testes isolated from hypothyroid rats is observed. This effect is more evident in thyroidectomized rats where a marked drop in the "in vitro" production of some testosterone delta 4 precursors is associated with the increase in DHEA/delta 4 ratio. T3 injection to thyroidectomized rats only partially restores the "in vitro" testosterone production. Results suggest that as the degree of hypothyroidism became more severe, the rate of testosterone production decreases and testicular steroidogenesis changes from the delta 4 to delta 5 metabolic pathway as a consequence of the impairement of 3-beta-ol-dehydrogenase activity.

Topics: Androstenedione; Animals; Body Weight; Dehydroepiandrosterone; Dihydrotestosterone; Glucosephosphate Dehydrogenase; Hypothyroidism; Male; Methimazole; Organ Culture Techniques; Organ Size; Phosphogluconate Dehydrogenase; Progesterone; Rats; Rats, Inbred Strains; Testis; Testosterone; Thyroidectomy; Triiodothyronine

Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Animals, Newborn; Benzazepines; Body Weight; Corpus Striatum; Dopamine; Dopamine Antagonists; Female; Homovanillic Acid; Hypothyroidism; Male; Methimazole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Reference Values; Synaptosomes; Thyroxine; Triiodothyronine; Tyramine

To evaluate the dose-response relationship between thyroxine and tibial growth, 60 male rats age 21 days were rendered hypothyroid by administration of methimazole in the drinking water. Twenty-one days later, the hypothyroid rats were randomly divided into 5 groups which received 0, 2, 8, 32, or 64 micrograms.kg-1.day-1 of T4 im for 21 days. All animals were sacrificed at age 64 days. Rat tibia were removed for measurement of epiphyseal growth plate width and longitudinal growth rate. Serum T4 and IGF-I levels were determined by RIA. Methimazole therapy significantly decreased serum T4, IGF-I, epiphyseal growth plate width, and longitudinal growth rate compared to controls. Epiphyseal growth plate width gradually increased when T4 was administered at doses from 2 to 32 micrograms.kg-1.day-1 (271 +/- 14, 311 +/- 15 and 324 +/- 11 microns), and subsequently decreased when T4 was given at a dose of 64 micrograms.kg-1.day-1 (267 +/- 8 microns). A similar profile was observed for longitudinal growth rate and IGF-I. We conclude that rat tibial growth has a biphasic response to exogenous T4 administration, and that the effects of T4 on tibial growth may be mediated through IGF-I secretion.

Topics: Animals; Body Weight; Bone Development; Eating; Growth Plate; Hypothyroidism; Insulin-Like Growth Factor I; Male; Methimazole; Rats; Rats, Inbred Strains; Thyroxine

Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and aldosterone were consecutively measured during methimazole treatment in patients with hyperthyroidism due to Graves' disease. ANP values of untreated hyperthyroid patients varied greatly from patient to patient, but decreased progressively with a decrease of serum thyroid hormone concentration during methimazole treatment. PRA was elevated in hyperthyroid patients but less aldosterone was secreted as evidenced by lower aldosterone/PRA ratio in these patients than in normal subjects and in hypertensive patients treated with thiazide. In addition, aldosterone/PRA ratio increased progressively with a decrease of ANP during methimazole treatment. The data indicated that ANP secretion was increased and ANP thus secreted depressed aldosterone secretion in hyperthyroid patients. Propranolol depressed pulse rate but failed to affect ANP secretion. It is suggested that thyroid hormone specifically acts on myocytes to stimulate ANP secretion but physiologic significance of such increased ANP secretion remains to be solved.

Topics: Adolescent; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Graves Disease; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propranolol; Pulse; Renin; Thiazines; Thyroid Gland

The relationship between thyroid activity and Sertoli cell function has been investigated in prepubertal rats. Male 28-day-old Wistar rats were used to prepare Sertoli cells by sequential enzyme digestion of the testes. Hypothyroidism, induced by oral administration of methimazole from the day of birth, was characterized by a severe retardation of body and testis growth and a net inhibition of the increase in Sertoli cell gamma-glutamyl transpeptidase (GGT) activity as well as in androgen-binding protein (ABP) and lactate production, which normally occur during postnatal development of Sertoli cells. The functional parameters of Sertoli cells from hypothyroid 28-day-old rats approximated to those of cells from euthyroid 15-day-old animals. These results are consistent with the impairment of protein synthesis in Sertoli cells from hypothyroid rats compared with controls. Body and testis growth were improved and Sertoli cell functions were restored with 3,3',5-tri-iodothyronine (T3) replacement therapy. An excess of T3 in the serum, induced by daily i.p. injections of T3 (100 micrograms/kg body wt) during the last week before the rats were killed, failed to induce changes in body and testis growth or in the activity of GGT and lactate dehydrogenase of Sertoli cells. Cells from hyperthyroid rats exhibited a specific decrease in ABP production. These results indicate that thyroid hormone is necessary for the postnatal maturation of Sertoli cell function and suggest a regulatory role of the hormone on gametogenic development in the prepubertal rat.

Topics: Aging; Androgen-Binding Protein; Animals; Body Weight; gamma-Glutamyltransferase; Hypothyroidism; L-Lactate Dehydrogenase; Lactates; Male; Methimazole; Organ Size; Rats; Rats, Inbred Strains; Sertoli Cells; Testis; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Adult; Body Weight; Energy Intake; Female; Humans; Hyperthyroidism; Male; Methimazole; Methylthiouracil; Middle Aged

The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain Chemistry; Cholecystokinin; Digestive System; Female; Hypothyroidism; Methimazole; Organ Size; Pregnancy; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

The effect of hypothyroidism on the thyrotropin-releasing hormone (TRH) receptors in several brain regions and pituitary of rats was determined. TRH receptors were labeled with 3H-(3-MeHis2)TRH (3H-MeTRH). Hypothyroidism was induced in male Sprague-Dawley rats by administering methimazole (0.05% w/v) in drinking water for 32 days. Rats serving as controls were given water without the methimazole. The development of a hypothyroid state was evidenced by significant decreases in colonic temperature, systolic blood pressure, heart rate and serum concentration of triiodothyronine (total T3), thyroxine and T3 uptake (T3U) as compared to control rats. The rate of gain in body weight of methimazole-treated rats was significantly lower than that of control rats. Binding of 3H-MeTRH at 2 nM concentration to membranes prepared from brain regions (striatum, hypothalamus, cortex, midbrain and pons plus medulla) of methimazole-treated and control rats did not differ. However, binding of 3H-MeTRH to pituitary membranes of methimazole-treated rats was significantly lower as compared to the pituitary of control rats. The results indicate that, in the rat, development of hypothyroidism is associated with down-regulation of pituitary TRH receptors but brain receptors remain unaffected.

Topics: Animals; Blood Pressure; Body Temperature; Body Weight; Brain; Brain Chemistry; Heart Rate; Hypothyroidism; Male; Methimazole; Pituitary Gland; Rats; Rats, Inbred Strains; Receptors, Thyrotropin

After demonstrating that prenatal exogenous thyroid hormone administration to pregnant rats produces decreases in fetal lung antioxidant enzyme (AOE) development despite increases in surfactant development, we examined the role of endogenous thyroid hormones on the development of these two lung systems. We administered the antithyroid drug methimazole (or diluent) to pregnant rats for the final 3 days before premature or term delivery; in a second series of experiments, propylthiouracil was administered for the 10 days before delivery. Both antithyroid drugs, known to cross the placenta, produced significantly decreased thyroid hormone levels in the pregnant dams. Fetal offspring from methimazole-, and propylthiouracil-treated dams demonstrated significant increases in pulmonary superoxide dismutase activity at 20 and 21 days of gestation and in catalase and glutathione peroxidase activities at 21 days compared with control offspring. Surfactant, measured as lung tissue disaturated phosphatidylcholine, was not different between either experimental group and controls. These results suggest that thyroid blockade increases AOE because the influence of thyroid hormone on AOE development may be one of depression. The findings confirm that certain hormonal regulators may influence different developing fetal lung systems in different ways.

Topics: Animals; Body Weight; Catalase; Female; Fetus; Gestational Age; Glutathione Peroxidase; Lung; Methimazole; Organ Size; Pregnancy; Propylthiouracil; Pulmonary Surfactants; Rats; Rats, Inbred Strains; Reference Values; Thyroid Gland; Thyroxine; Triiodothyronine

Hypothyroidism was induced in young female Sprague-Dawley rats by the addition of methimazole (0.67 mg/ml) to drinking water for a period of 7 weeks (7-14 weeks of age). The responses of the articular cartilage, epiphyseal growth plate cartilage, epiphyseal trabecular bone, and metaphyseal trabecular bone in the proximal tibia were assessed by structural parameters. In addition, replacement therapies were introduced for the last 2 weeks of the experimental period. These included 0.7 U/kg BW human GH (hGH), 15 micrograms/kg BW L-T4 (T4), and a combination of hGH and T4 at the same doses. In the hypothyroid rats, the width of epiphyseal growth plate cartilage decreased by 27%, that of articular cartilage by 35%, epiphyseal trabecular bone volume by 30%, and metaphyseal trabecular bone volume by 66% relative to those in age-matched control tissues. T4 treatment led to a full restoration of the epiphyseal trabecular bone and surpassed by 40% the control value. The magnitude of the articular cartilage and the epiphyseal trabecular bone volume returned to control values, while that of metaphyseal trabecular bone was 68% of control values. Treatment with hGH did not improve the epiphyseal growth plate cartilage or articular cartilage. It did restore epiphyseal trabecular bone to almost normal values, but metaphyseal trabecular bone improved to only a small though significant level (45% of control value). The combination of T4 and hGH resulted in an additional enlargement in the width of the epiphyseal growth plate cartilage and an increase in metaphyseal trabecular bone volume compared to those in the T4 group. Qualitative examinations indicated that it was only in the T4 and T4 plus hGH groups that the lowest chondrocytes in the epiphyseal growth plate cartilage resumed their normal hypertrophied size. These results suggest that the change in the hypothyroid state do not rely solely on the lack of pituitary GH synthesis and secretion, as replacement by exogenous GH did not restore normal epiphyseal growth plate cartilage morphology or its remodeling into metaphyseal trabecular bone. Treatment with T4 (which restored endogenous pituitary GH to 30% of control levels) results in full recovery of the epiphyseal growth plate cartilage morphology along with its associated metaphyseal trabecular bone. In addition, it can also be concluded that the decrease in epiphyseal trabecular bone volume observed in the hypothyroid animals was due solely to the GH-deficient state

Topics: Animals; Body Temperature; Body Weight; Bone and Bones; Bone Development; Female; Growth Hormone; Growth Plate; Hypothyroidism; Methimazole; Rats; Rats, Inbred Strains; Reference Values; Thyroxine

The effect of chronic administration of methimazole (0.05% w/v) in drinking water for 32 days to male Sprague-Dawley rats on the binding of opioid ligands, 3H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu-receptors), 3H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta-receptors) and 3H-ethylketocyclazocine (EKC, kappa-receptors) to membranes of brain regions was determined. Chronic administration of methimazole to rats decreased their rate of body weight gain, colonic temperature, systolic blood pressure and heart rate in comparison to vehicle-treated rats. Administration of methimazole also decreased the serum concentration of triiodothyronine (total T3) and T4 when compared to vehicle-treated rats. The binding of 3H-DAGO to membranes of amygdala, pons and medulla, striatum, midbrain and cortex of methimazole-treated rats was greater than vehicle-treated rats, however, the binding to membranes of hypothalamus in the two treatment groups did not differ. The binding of 3H-DSTLE in amygdala and hypothalamus of methimazole-treated rats did not differ but it was significantly greater in pons and medulla, midbrain, cortex and striatum of methimazole-treated rats than vehicle-treated rats. The binding of 3H-EKC to membranes of pons and medulla was lower and of striatum and cortex of methimazole-treated rats was significantly greater than vehicle-treated rats, but the binding to membranes of amygdala, hypothalamus, and midbrain of the two treatment groups did not differ. The results indicate that brain, mu-, delta- and kappa-opioid receptors are differentially altered in hypothyroidism.

Topics: Animals; Body Temperature; Body Weight; Brain Chemistry; Cyclazocine; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalins; Ethylketocyclazocine; Heart Rate; Hypothyroidism; Male; Methimazole; Oligopeptides; Rats; Rats, Inbred Strains; Receptors, Opioid; Triiodothyronine

Male Sprague-Dawley rats were treated ip on Day 0 with 0, 20, 50, or 100 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and biliary tree permeability was evaluated on Days 2, 4, 7, 10, 14, or 20 by segmented retrograde intrabiliary injection of [3H]sucrose or [14C]mannitol. Seven days after 100 micrograms/kg TCDD, the percentage recovery in bile of both [3H]sucrose (73.9 +/- 4.2 vs 27.6 +/- 7.6, control vs TCDD, means +/- SE) and [14C]mannitol (22.7 +/- 2.2 vs 12.1 +/- 2.2) was decreased, demonstrating that the permeabilities of both the intracellular (canalicular) and paracellular pathways were increased. Seven days after 50 micrograms/kg TCDD, the recovery of [3H]sucrose was decreased (73.5 +/- 5.4 vs 39.0 +/- 2.8) but the recovery of [14C]mannitol was not (25.5 +/- 1.5 vs 22.9 +/- 1.9). Thus, an increase in paracellular permeability is obtained at a lower dose of TCDD. In rats treated with 100 micrograms/kg TCDD on Day 0, co-treatment with chlordecone (15 mg/kg/day on Days 2-6) or thyroxine (50 micrograms/kg on Day 2) had no effect. Pregnenolone-16 alpha-carbonitrile (75 mg/kg/day on Days 4-6) treatment increased [14C]mannitol recovery in both TCDD and control groups; its effect must not be specific. Methimazole given in drinking water (0.5%) on Days -7 through 7 reversed the increased permeability effects of TCDD (100 micrograms/kg) without affecting the biliary tree permeability ([14C]mannitol recovery) of control animals.

Topics: Animals; Biliary Tract; Body Weight; Chlordecone; Dioxins; Food Deprivation; Liver; Male; Mannitol; Methimazole; Permeability; Polychlorinated Dibenzodioxins; Pregnenolone Carbonitrile; Rats; Rats, Inbred Strains; Sucrose; Thyroxine

The induction of hypothyroidism by methimazole produces a delay in CNS development as well as behavioral deficits in rat pups. Methimazole (0.1 mg/ml) was administered via drinking water to dams from gestational day 17 to postnatal day 10. Rat pup body weight was reduced on postnatal day 15 (P15) and 30 (P30) while brain weight was decreased only at P15. Soluble brain protein was decreased at P15 and P30. Total enolase and neuron-specific plus hybrid enolase (NSE+H) specific activity and activity were reduced on P15, while non-neuronal enolase (NNE) activity but not specific activity was depressed. At postnatal day 30, total enolase and NSE+H activity were slightly reduced, but NNE activity and the specific activities of total enolase, NNE and NSE+H were similar to controls. The ratio of NSE+H to NNE was reduced at P15 but not P30. The alterations in enolase activity following methimazole administration suggest a delay in the development and maturation of the CNS at P15. These results provide a biochemical correlate of the developmental delays reported in hypothyroid rat pups.

Topics: Age Factors; Animals; Body Weight; Brain; Female; Fetus; Hypothyroidism; Isoenzymes; Methimazole; Organ Size; Phosphopyruvate Hydratase; Pregnancy; Rats; Rats, Inbred Strains

The pituitary of goitrogen-treated White Leghorn cockerels is smaller in size than control birds and the pituitaries of castrated cockerels is nearly twice the size of control birds. The pituitary cells generated by these treatments may not be functional thyrotrophs or gonadotrophs and may not be able to respond to their usual stimuli. Low ambient temperature is a well-known stimulus to the thyroid gland acting through pituitary TSH. Cyclic-AMP-dependent protein kinase activity levels are used here as an index of cellular activity in the pituitary and thyroid glands. Castrated cockerels with or without methimazole treatment do not have an increased pituitary cAMP-dependent protein kinase activity in cold. Methimazole-treated birds have an exaggerated pituitary protein kinase response to cold stress when compared with controls. Pituitary cAMP-dependent protein kinase activity is paralleled by a similar activity increase in the thyroid gland of methimazole-treated cockerels and no increase in the thyroid of castrated birds. Castrated birds at all temperatures have an elevated thyroid cAMP-dependent protein kinase activity ratio which is interpreted as the result of removal of testosterone inhibition.

Topics: Animals; Body Weight; Castration; Chickens; Cyclic AMP; Male; Methimazole; Organ Size; Pituitary Gland; Protein Kinases; Temperature; Thyroid Gland

The long-term effects of perinatal hypothyroidism on spontaneous locomotor behaviors were assessed after exposure to the antithyroid drug, methimazole. Perseveration was observed in methimazole-treated rats in a spatial maze. Locomotor activity in residential mazes was examined at 6 weeks, 4 months, and 6 months of age. Treated rats were hypoactive at some intervals compared with controls and were hyperactive at others. These paradoxical differences resulted from changes in exploratory, diurnal, and nocturnal locomotor activity in control rats both with increasing age and on repeated exposures to residential mazes; rats after perinatal hypothyroidism had relatively constant levels of activity on repeated days of exposure to residential mazes and at different ages. These results may be related to perseveration noted in the spatial maze. In an analysis of walking patterns, treated rats tended to have a more pronounced asymmetry in gait than controls.

Topics: Animals; Behavior, Animal; Body Weight; Exploratory Behavior; Female; Hypothyroidism; Methimazole; Motor Activity; Pregnancy; Rats; Rats, Inbred Strains; Sex Factors

Cockerels and pullets fed with T3 or T4 for 2 weeks showed a decrease in both body weight gain and feed efficiency. The reduction in body weight gain and feed efficiency was dose related in cockerels where T3 or T4 were fed at 0.1, 1.0, and 10.0 ppm levels. T3 and T4 at 0.1 and 1.0 ppm had no significant effects on growth or feed efficiency in pullets, but the 10.0-ppm level of T3 and T4 caused a reduction of -55.24 and -28.18%, respectively, in body weight gain as compared with control birds. T3 was more active than T4 in reducing growth and was toxic when fed at 10.0 ppm both in cockerels and pullets. Both propylthiouracil (PTU)- and methimazole-treated cockerels showed a decrease in rates of gain. T3 and T4 at a dietary level of 0.1 ppm were equipotent in promoting growth in these PTU- and methimazole-treated cockerels, but 10.0 ppm caused a further reduction in body weight gain. Plasma T3 levels were found to be significantly higher in birds that were fed either T3 or T4. Plasma T4 levels were higher in T4-fed birds, but significantly lower in T3-fed birds as compared with controls. Both PTU- and methimazole-treated cockerels had significantly lower plasma T3 and T4 concentrations, but elevated plasma GH concentrations. Dietary T3 and T4 at 1.0 and 10.0 ppm significantly lowered plasma GH concentrations. In summary, these results indicated that T3 was more active than T4 in reducing body weight gain in intact normal birds, but that they were equally potent in promoting growth in PTU- and methimazole-treated hypothyroid birds.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Chickens; Diet; Female; Growth; Growth Hormone; Hypothyroidism; Male; Methimazole; Propylthiouracil; Thyroxine; Triiodothyronine

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Female; Fetus; Male; Methimazole; Motor Activity; Nervous System; Pregnancy; Rats; Rats, Inbred Strains; Reflex; Reflex, Startle

Topics: Animals; Body Weight; Goiter; Hypothyroidism; Iodide Peroxidase; Isoenzymes; Kinetics; Liver; Male; Methimazole; Peroxidases; Rats; Thyroid Gland; Thyroid Hormones; Thyrotropin

The absence of the thyroid stimulation of hepatic [Na+ + K+]ATPase in obese (ob/ob) mice has been investigated. A wide range of tri-iodothyronine (T3) concentrations failed to enhance the hepatic [Na+ + K+]ATPase of ob/ob mice made hypothyroid by methimazole treatment but glycerophosphate dehydrogenase activity was maximally stimulated at low doses of T3. Adrenalectomy increased the basal activity of [Na+ + K+]ATPase to levels found in lean control mice and restored the response of this enzyme to T3. Body weight gain was unaffected by the induction of hypothyroidism in either lean or ob/ob mice. It is concluded that the adrenal steroids play an important role in the expression of [Na+ + K+]ATPase activity in the ob/ob mouse.

Topics: Adrenalectomy; Animals; Body Weight; Glycerolphosphate Dehydrogenase; Hypothyroidism; Liver; Methimazole; Mice; Mice, Obese; Sodium-Potassium-Exchanging ATPase; Triiodothyronine

This study examines the relation between whole body O2 requirements and lung growth. 6-week-old hamsters were exposed to cold (5 degrees C) or injected with thyroid hormone. These treatments elevated O2 consumption by 26% over a 28-day period. Both alveolar surface area and total lung air volume were increased by approximately 25% in each group. Morphometric data suggest that lung enlargement was due to an increase in the number or complexity, rather than size of individual alveolar units. Further elevating O2 demand by increasing thyroid dosage did not enhance lung size beyond the level observed with the lowest dose used. Depressing metabolic rate with an antithyroid drug for four weeks had no effect on lung structure (in this animal model). Results indicate that in hamsters, increased physiologic O2 demand may be met to a certain extent by augmentation of the pulmonary diffusing surface.

Topics: Animals; Body Weight; Cold Temperature; Cricetinae; Lung; Male; Methimazole; Organ Size; Oxygen Consumption; Pulmonary Alveoli; Thyroid Hormones

Topics: Animals; Body Weight; DNA; Dose-Response Relationship, Drug; Heart; Hypothyroidism; Methimazole; Myocardium; Rats; RNA

Mutagenicity test of Methimazole (MMI) was performed by means of dominant lethal mutation test in the male mice. Male mice were treated with a single s.c. injection of 45 mg/kg or 90 mg/kg MMI. Mean body weights were slightly decreased and mating rates were low immediately after treatment of MMI. Mean numbers of living implants at any periods examination up to 6 weeks after the treatment were compared with Salin Control, indicating lack of dominant lethality of MMI. On the other hand, EMS and MMC known mutagens and reference agents used in the present study, induced dominant lethalities at a single s.c. injection respectively.

Topics: Animals; Body Weight; Ethyl Methanesulfonate; Female; Genes, Dominant; Genes, Lethal; Gestational Age; Male; Methimazole; Mice; Mitomycins; Mutagens; Organ Size; Pregnancy

An account is given of incidence, diagnosis, therapy, and clinical peculiarities of hyperthyreosis in gravidity, with reference being made to literature as well as to the authors' own experience. It is strongly suggested that thyreostatic treatment may yield good success even under the conditions of gravidity, provided that certain peculiarities are taken into due consideration. Conclusions then are drawn for efficient organisation of medical attention to pregnant patients with thyroid diseases.

Topics: Abortion, Spontaneous; Body Weight; Female; Fetal Diseases; Fetus; Humans; Hyperthyroidism; Meningocele; Methimazole; Pregnancy; Pregnancy Complications; Thyroid Hormones

The effects of feeding a heat treated rapeseed meal, which has goitrogenic properties, on the concentrations of plasma pituitary and thyroid gland hormones was investigated in broiler cockerels of between 3 and 10 weeks of age. For purposes of comparison, two other groups were included in the study; one was fed the goitrogen, methimazole, and the other a normal control diet. The hormones measured were thyroxine (T4), triiodothyronine (T3), growth hormone (GH), prolactin, and luteinizing hormone (LH). In birds fed methimazole the thyroid glands were greatly enlarged, the concentrations of plasma T4 and T3 were depressed and the concentrations of growth hormone, prolactin, and LH were elevated. The high level of plasma LH in the birds fed methimazole was not due to the absence of sufficient concentrations of plasma testosterone to exert a negative feedback effect. Although the inclusion of rapeseed meal in the diet caused the thyroid glands to enlarge, the concentrations of all the hormones studied, with the exception of T3, were similar to those in the control birds. However, there was a tendency, which was more pronounced in birds of between 3 and 5 weeks of age, for rapeseed meal to depress the concentrations of plasma T4, GH, and LH and to increase the concentration of plasma prolactin. The most significant observation was that between 3 and 5 weeks of age the inclusion of rapeseed meal in the diet significantly (P less than .001) depressed the concentration of plasma T3.

Topics: Age Factors; Animals; Body Weight; Brassica; Chickens; Growth Hormone; Luteinizing Hormone; Male; Methimazole; Organ Size; Pituitary Hormones, Anterior; Prolactin; Testosterone; Thyroid Hormones; Thyroxine; Triiodothyronine

Topics: Adenylyl Cyclases; Animals; Body Weight; Male; Methimazole; Organ Size; Phospholipids; Propylthiouracil; Rats; Thyroid Gland

Isolated terminal colon strips obtained from rats, made hypothyroid by methimazole treatment, were almost completely insensitive to the contractile effects of morphine as compared to strips from control animals. This low morphine sensitivity was accompanied by a significant (40%) reduction in the tissue sulfatide content. Although colon strips from hypothyroid rats showed a reduction of the contractile effects of acetylcholine, the decrease was considerably less than that noted for morphine. The addition of 6.6 X 10(-5) M tri-iodothyronine to colons from hypothyroid rats largely restored the tissue sensitivity to morphine. These results suggest that sulfatides could be linked to the in vitro effects of morphine in the colon.

Topics: Acetylcholine; Animals; Body Weight; Colon; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Morphine; Muscle Contraction; Muscle, Smooth; Rats; Sulfoglycosphingolipids

Topics: Aging; Animals; Body Height; Body Weight; Chick Embryo; Chickens; Diet; Male; Methimazole; Muscles; Organ Size; Propylthiouracil; Triiodothyronine

Topics: Animals; Body Weight; Dermatitis; Diet; Dose-Response Relationship, Drug; Iodine Radioisotopes; Isothiocyanates; Methimazole; Organ Size; Rats; Thiocyanates; Thyroid Function Tests; Thyroxine; Triazoles; Triiodothyronine

Topics: Animals; Body Weight; Cold Temperature; Heart; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Kinetics; Male; Methimazole; Muscles; Myocardium; Norepinephrine; Organ Size; Rats; Thyroid Hormones; Thyroidectomy; Thyroxine; Time Factors

Further examination of rat pituitary cell line GH3/C14 showed that at least the physiologic concentration of L-thyroxine was required for estrogen-dependent growth in vivo. Two L-thyroxine synthesis inhibitors, 6-n-propyl-2-thiouracil (propylthiouracil) and 1-methylimidazole-2-thiol (methimazole), were administered concurrently with estrogen to GH3/C14-inoculated hosts. Propylthiouracil administration to estrogen-treated males, intact females, and estrogen-treated ovariectomized females inhibited tumor formation by 93, greater than 95, and 68%, respectively, as compared to tumor formation in controls not treated with propylthiouracil. Methimazole treatment of estrogen-primed males and intact females inhibited tumor formation by 78 and 95%, respectively. Concentrations of total L-thyroxine and free L-thyroixine in sera from normal and inhibitor-treated hosts were depressed 70-80% by propylthiouracil and 60-70% by methimazole. Administration of either drug caused greater inhibition of tumor growth than of total body weight gain. In addition, the administration of a combination of L-thyroxine and L-triiodothyronine to male rats promoted tumor formation even in the absence of exogenous estrogen.

Topics: Animals; Body Weight; Castration; Cell Division; Cell Line; Estrogens; Female; Male; Methimazole; Neoplasms, Experimental; Ovary; Pituitary Neoplasms; Propylthiouracil; Rats; Rats, Inbred WF; Thyroxine

Epidemiological findings from the city of Cali, Colombia, support the hypothesis that water supply and iodine intake are not the only dietary factors which influence the magnitude of the goitre endemia. Experiments were conducted in rats to determine whether casein has a counteracting effect on the goitrogenic and antithyroid activities of methimazole (MMI) and goitrogenic water extracts (GWE) from the endemic area of the Cauca Valley. Female albino rats (Charles River, DC strain) 100-110 g initial weight, receiving 12 mug of iodine daily, were divided into three groups annd put on special diets: protein-free, 8 % casein, or 60 % casein, respectively. Each group (24 rats) was then divided into three subgroups. Subgroup one received goitrogen-free water and was used as a control. Subgroup two was administered MMI, 50 mug/day/rat. Subgroup three was given per animal a daily amount of GWE equivalent in antithyroid potency to 50 mug of MMI. At 77 days, the thyroid glands were studied for weight, 131I uptake, and 127I concentration. Animals on the protein-free diet showed significantly (P less than 0.05 - less than 0.01) larger thyroid glands per 100 g body weight and lower thyroidal 4 h 131I uptake and 127I-concentrations than rats on casein diets. These differences were significantly increased (P less than 0.01) by the administration of MMI and GWE. All the effects were completely reversed by the 60 % casein diet showing no differences between control rats and those on MMI or GWE. Rats on 8 % casein showed intermediate values between those of animals on protein-free and 60 % casein diets; differences were still present between the control as against the MMI or GWE groups, The results indicate that under these experimental conditions, a poor-protein diet impairs the thyroidal transport of iodine, decreases its concentration in the thyroid and is accompanied by an enlargement of the gland. Under these circumstances, the action of thiourea-like antithyroid agents is enhanced. The administration of protein reverses these alterations and decreases the action of such antithyroid agents. Whether the changes observed are due to a direct action of casein on the thyroid and/or to effects of malnutrition on the metabolism of antithyroid compounds remains to be determined.

Topics: Animals; Body Weight; Caseins; Dietary Proteins; Drug Evaluation, Preclinical; Female; Goiter; Iodine; Methimazole; Organ Size; Rats; Thyroid Gland

Elimination of 137-Cs and 59-Fe by three species of wild rodents was measured in laboratory and field experiments to determine whether excretion rates of these nuclides are influenced directly by general metabolic (CO-2 production) rates. Sigmodon hispidus and Peromyscus leucopus were used in both field and laboratory experiments, and Reithrodontomys humulis was investigated only in the laboratory. Final-component biological half-lives (Tb) of 59-Fe for Sigmodon averaged 108 days in winter, 144 days in spring, and means ranged from 176 to 242 days under various laboratory conditions (ambient temperature, cold-exposure, irradiation, and chemical metabolic inhibition); for Peromyscus, values were 50 days in winter 47 days in spring, and 289 days (at ambient temperature only) in the laboratory; for Reithrodontomys mean values ranged from 121 to 178 days at different laboratory treatment levels. Biological half-lives of final-component 137-Cs elimination for Sigmodon averaged 7.5 days in winter, 7.9 days in spring, and means ranged from 7.7 to 8.6 days at the different treatment levels in the laboratory. Laboratory mean values for Reithrodontomys ranged from 3.5 to 3.9 days. For Peromyscus, Tb values averaged 3.4 days in winter, 3.6 days in spring, and 3.5 days in the laboratory. The data suggested that elimination of 59-Fe is influenced by metabolic rates of rodents in the field, but laboratory experiments were unable to demonstrate any predictable relationship. Neither did the rate of final-component 137-Cs loss from rodents appear to be influenced by metabolic rate in the laboratory or in the field. However, final-component Y-axis intercept values of 137-Cs exhibited a linear correlation with metabolic rates, and equations were derived from these intercept values to predict metabolism in the field for two species: for Sigmodon, Daily Average CO-2 Production (ml/hr/g, STP) [5.24-0.9172 (log-ea)] [0.886]; and for Reithrodontomys, = [12.51-1.80 (log-ea)] [0.886].

Topics: Animals; Body Weight; Carbon Dioxide; Cesium; Cesium Radioisotopes; Cold Temperature; Injections, Intraperitoneal; Iron; Iron Radioisotopes; Methimazole; Mice; Rats; Rodentia; Seasons; Temperature; Thyroid Gland

Thyroid activity of both male and female spontaneous hypertensive (SH) rats was studied by measurements of uptake and rate of release of 131-I, urinary excretion of 131-I, and thyroxine secretion rate (TSR). In addition, thyroid glands were removed at death and weighed. Radioactivity of the thyroid gland of male rats measured at intervals after administration of 131-I revealed a significantly reduced maximal uptake at 21.5 hr after injection and a reduced rate of release. The mean biological half-life of 131-I for the control group was 37.8 plus or minus 3.1 (SE) hr compared to 54.8 plus or minus 7.2 hr for hypertensives (P less than 0.05). Similar results were observed for females in that biological half-life of 131-I was 32.2 plus or minus 1.2 hr compared with 84.1 plus or minus 4.1 hr for hypertensives (P less than 0.01). Urinary excretion of 131-I by hypertensive rats at 24, 48, and 72hr after injection of 131-I did not differ from control in either experiment. Thyroid weight at autopsy was increased significantly above that of normotensive controls. TSR was measured indirectly in a third group of male spontaneously hypertensive and normotensive rats. TSR of control rats was estimated to be 0.97 mug T4/100 g body wt/day and 1.35 mug T4/100 g body wt/day for SH RATS. The results are consistent with the suggestion that the method for measurement of TSR in hypertensive rats gives an artifactually high value because TSH secretion is elevated.

Topics: Animals; Body Weight; Chick Embryo; Female; Hypertension; Injections, Intraperitoneal; Iodine; Iodine Radioisotopes; Male; Methimazole; Organ Size; Rats; Thyroid Gland; Thyroxine; Time Factors

Topics: Administration, Oral; Animal Feed; Animals; Antithyroid Agents; Body Weight; Caseins; Dietary Proteins; Female; Glycine max; Hypothyroidism; Iodine; Iodine Radioisotopes; Male; Methimazole; Organ Size; Plant Proteins, Dietary; Protein Binding; Swine; Swine Diseases; Thiocyanates; Thyroid Gland; Time Factors

Topics: Animals; Body Weight; Dihydroxyphenylalanine; Humans; Hypothyroidism; Male; Methimazole; Mice; Organ Size; Pituitary Gland; Radioimmunoassay; Rats; Species Specificity; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Actins; Animals; Body Height; Body Weight; Chick Embryo; DNA; Hypothyroidism; Methimazole; Muscle Development; Muscle Proteins; Muscles; Organ Size; Thyroid Gland; Thyroxine; Time Factors

Topics: Analysis of Variance; Animals; Body Weight; Chickens; Female; Genes; Genotype; Iodine Radioisotopes; Male; Methimazole; Organ Size; Seasons; Secretory Rate; Sex Factors; Thyroid Gland; Thyrotropin; Thyroxine

Topics: Animals; Biological Assay; Body Weight; Diet; Kidney; Male; Methimazole; Rats; Thyroid Gland; Thyroxine; Transaminases

Topics: Animals; Animals, Newborn; Body Weight; Brain; Brain Chemistry; Carbon Radioisotopes; Cerebrosides; Chromatography, Thin Layer; Fatty Acids; Galactose; Glycolipids; Hypothyroidism; Lipids; Methimazole; Organ Size; Rats; Sphingomyelins; Sulfoglycosphingolipids; Uridine Diphosphate Sugars

Topics: Animals; Body Weight; Calcitonin; Calcium; Female; Iodine Isotopes; Methimazole; Pituitary Gland; Rats; Rats, Inbred Strains; Secretory Rate; Thyroid Gland; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Acclimatization; Adrenal Glands; Animals; Body Temperature Regulation; Body Weight; Catecholamines; Cold Temperature; Epinephrine; Glycols; Hot Temperature; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Myocardium; Norepinephrine; Normetanephrine; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroxine; Time Factors

Topics: Animals; Biological Assay; Blood Proteins; Body Weight; Chickens; Goiter; Hybrid Vigor; Hybridization, Genetic; Iodine; Methimazole; Organ Size; Protein Binding; Secretory Rate; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Thyroxine

Topics: Animals; Antithyroid Agents; Blood Proteins; Body Weight; Goiter; Hypothyroidism; Insulin; Iodine; Male; Methimazole; Organ Size; Perchlorates; Propylthiouracil; Protein Binding; Rats; Rhenium; Thiocyanates; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine

Topics: Animals; Animals, Newborn; Body Weight; Female; Growth; Iodine Radioisotopes; Male; Methimazole; Rats; Reproduction; Sexual Behavior, Animal; Thiouracil; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Age Factors; Animals; Antithyroid Agents; Blood Pressure; Body Weight; Dinitrophenols; Female; Hypertension; Imidazoles; Male; Methimazole; Rats; Sodium Chloride; Stimulation, Chemical; Thyroidectomy; Triiodothyronine

Topics: Animals; Animals, Newborn; Antithyroid Agents; Body Weight; Brain; Centrifugation; Cerebrosides; Cholesterol; Chromatography; Hydrocortisone; Hypothyroidism; In Vitro Techniques; Lipids; Methimazole; Myelin Sheath; Organ Size; Rats; Sulfates; Sulfur Isotopes; Thyroid Gland; Thyroidectomy; Transferases; Triiodothyronine

Topics: Antithyroid Agents; Body Weight; Iodine Isotopes; Methimazole; Organ Size; Perchlorates; Pharmacology; Pituitary Gland; Pituitary Hormones, Anterior; Propylthiouracil; Rats; Research; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Toxicology

Topics: Animals; Antithyroid Agents; Biological Phenomena; Body Weight; Body Weights and Measures; Chick Embryo; Embryo, Mammalian; Embryo, Nonmammalian; Growth; Methimazole; Physiological Phenomena; Thyroid Gland

Topics: Animals; Antithyroid Agents; Body Weight; Cattle; Methimazole; Thyroid Gland