glycogen and Hypothyroidism

Hypothyroidism during pregnancy is associated with fetal growth restriction (FGR). FGR is commonly caused by placental insufficiency and yet the role of hypothyroidism in placental regulation of fetal growth is unknown. This study aimed to investigate the effects of maternal hypothyroidism on placental nutrient transporter expression, placental morphology, and placental metabolism.. Hypothyroidism was induced in female Sprague-Dawley rats by adding methimazole (MMI) to drinking water at moderate (MOD, MMI at 0.005% w/v) and severe (SEV, MMI at 0.02% w/v) doses from one week prior to pregnancy and throughout gestation. Maternal and fetal tissues were collected on embryonic day 20 (E20).. Hypothyroidism reduced fetal weight (P. Overall, maternal hypothyroidism may lead to FGR through reduced maternal T4 availability, changes to placental morphology, altered nutrient transporter expression and sex-specific effects on placental metabolism. Changes to LZ glycogen and triglyceride stores as well as mitochondrial content suggest a metabolic shift from oxidative phosphorylation to anaerobic glycolysis in males. These changes also likely impact fetal substrate availability and therefore fetal growth.

Topics: Animals; Female; Fetal Development; Fetal Growth Retardation; Glycogen; Hypothyroidism; Male; Nutrients; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley

Hypothyroidism affects the content of triacylglycerol (TAG), total cholesterol (TC), oxidized lipids, glycogen, and infiltration of immune cells into the ovary and uterus. This study aimed to analyze the impact of hypothyroidism on the lipid content of different regions of the oviduct. Control (n = 6) and hypothyroid (n = 6; 10 mg/kg/day of methimazole in the drinking water for 30 days) adult rabbits were used. In the fimbriae/infundibulum (FIM/INF), ampulla, (AMP), isthmus (IST), and utero-tubal junction (UTJ), the TAG and TC concentrations, presence of oxidized lipid, relative expressions of perilipin A (PLIN A), peroxisome proliferator-activated receptor γ (PPARγ), CAAT/enhancer-binding protein α (C/EBPα), and farnesoid X receptor (FXRα) were analyzed. The content of glycogen and glycans, as well as the infiltration of lymphocytes, were also quantified. In the FIM/INF, hypothyroidism reduced the content of TC, expression of C/EBPα, and presence of glycans while increased the number of intraepithelial lymphocytes. In the AMP and IST-UTJ regions, hypothyroidism increased the content of TAG, oxidized lipids, expression of PPARγ, and glycogen content but decreased the expression of PLIN-A. The FXRα expression in secretory cells of IST-UTJ was higher in the hypothyroid rabbits compared to controls. Additionally, hypothyroidism reduced the C/EBPα expression and the number of intraepithelial lymphocytes in the AMP and IST-UTJ regions, respectively. We demonstrated that the effect of hypothyroidism depends on the oviductal region, possibly associated with different physiological functions specific to each region. These alterations may be related to infertility, tubal disturbances, and ectopic pregnancy observed in hypothyroid women.

Topics: Animals; Antithyroid Agents; Fallopian Tubes; Female; Glycogen; Hypothyroidism; Lipid Metabolism; Lipids; Lymphocytes; Methimazole; Rabbits

Topics: Animals; Cardiomegaly; Crosses, Genetic; Enzyme-Linked Immunosorbent Assay; Fever; Gene Expression Profiling; Glycogen; Heart Rate; Hypothyroidism; Lipolysis; Liver; Male; Mental Retardation, X-Linked; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Phenotype; Telemetry; Thermogenesis; Thermography; Thyroid Hormones; Time Factors; Triiodothyronine

Dyslipidaemia and hyperglycaemia are associated with ovarian failure and both have been related to hypothyroidism. Hypothyroidism promotes anovulation and ovarian cysts in women and reduces the size of follicles and the expression of aromatase in the ovary of rabbits. Considering that ovarian steroidogenesis and ovulation depend on lipid metabolism and signalling, the aim of the present study was to analyse the effect of hypothyroidism on the lipid content and expression of peroxisome proliferator-activated receptor (PPAR) δ in the ovary. Ovaries from female rabbits belonging to the control (n=7) and hypothyroid (n=7) groups were processed to measure total cholesterol (TC), triacylglycerol (TAG) and glycogen content, as well as to determine the presence of granules containing oxidized lipids (oxysterols and lipofuscin) and the relative expression of perilipin A (PLIN-A) and PPARδ. Hypothyroidism increased TC and glycogen content, but reduced TAG content in the ovary. This was accompanied by a reduction in the expression of PLIN-A in total and cytosolic extracts, changes in the presence of granules containing oxidative lipids and low PPARδ expression. The results of the present study suggest that hypothyroidism modifies the content and signalling of lipids in the ovary, possibly affecting follicle maturation. These results could improve our understanding of the association between hypothyroidism and infertility in females.

Topics: Animals; Cholesterol; Disease Models, Animal; Female; Glycogen; Hypothyroidism; Immunoblotting; Lipid Metabolism; Ovary; Perilipin-1; PPAR delta; Rabbits; Triglycerides

Background Iodine is a nonpareil constituent of thyroid hormones (THs) and a prime regulator of thyroid gland functioning. Although essential at recommended levels for the prevention of iodine deficiency disorders (IDDs), exposure to excess iodine reportedly causes hypothyroidism, hyperthyroidism, and several other emerging deleterious impacts. The objective of the present study is to explore the influence of excess iodide exposure on carbohydrate and lipid metabolism along with the histoarchitecture of certain associated organs such as the pancreas, liver, kidney, and skeletal and cardiac muscle because information on those aspects was found to be scanty. Methods Twelve rats were taken, six were fed with iodine through gavage at a dose of 3.5 mg potassium iodide (KI)/100-g body weight, which corresponded to 500 times of the physiological daily dosage of iodide for a period of 60 days, while the other six formed the control group. Results KI-treated rats presented high body weight and urinary iodine with low TH levels, suggesting a primary thyroid dysfunction. There was an increase in blood glucose, cholesterol, triglycerides, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), while high density lipoprotein (HDL) levels decreased. Tissue glycogen content in the liver and skeletal muscle was decreased and was increased in the heart and kidney. Histological sections of the pancreas showed a complete disruption with hardly recognizable histoarchistructure. Treated liver sections displayed the broadened central vein with degenerated hepatocytes, while skeletal muscle sections showed dissolution of muscle fibre cells linked with loss of glycogen from these organs. Histological changes in the heart include features similar to those of a fatty heart with cardiac muscles mutilation, while that of the kidney shows an increase in glomerular tuft size and Bowman's space expansion with general deterioration. Conclusions It may thus be concluded that excess iodine exposure for a long duration causes the development of a biochemical state of hypothyroidism. The developed hypothyroidism was found responsible for the hyperglycaemic and hypercholestromic status evident by high blood glucose and cholesterol levels and the depletion of glycogen at its storage sites in the liver and skeletal muscle but the extra deposition in the cardiac muscle and kidney; histomicrophotographs showed severe destruction of the pancreatic structure. All these alterations

Topics: Animals; Blood Glucose; Body Weight; Carbohydrate Metabolism; Drug Overdose; Glycogen; Hypercholesterolemia; Hyperglycemia; Hypothyroidism; Lipid Metabolism; Male; Potassium Iodide; Rats; Rats, Wistar; Thyroid Hormones; Time Factors

The objective of this study was to evaluate fetal weight, histomorphometric changes and proliferative activity, apoptosis and angiogenesis of the placenta in rats with hypothyroidism. Thirty-six adult female rats were divided into two groups with 18 animals each: control and hypothyroidism. Hypothyroidism was induced by daily administration of propylthiouracil (1 mg/animal). The administration began five days before becoming pregnant and the animals were sacrificed at 14 or 19 days of gestation. The control group received a placebo. The number and weight of fetuses and the rate of fetal death was determined, as well as the morphometric characteristics, the immunohistochemical expression of cell division control protein 47 (CDC)-47 and vascular endothelial growth factor (VEGF) and the number of apoptotic cells in the placental disk. The data were analysed by Mann-Whitney U test. Hypothyroidism reduced the weight of fetuses and of the uterus and placenta (P<0.05), altered the thickness of the placental labyrinth and spongiotrophoblast (P<0.05), increased the population of glycogen cells in the spongiotrophoblast (P<0.05), interfered with the vascular development of the placental labyrinth and decreased VEGF expression (P<0.05), reduced the expression of CDC-47 and cellularity and increased the apoptotic rate in the placental disk (P<0.05). We conclude that hypothyroidism affects fetal weight by altering the proliferative activity, apoptosis and vascularisation of the placenta.

Topics: Adenosine Triphosphatases; Animals; Apoptosis; Biomarkers; Cell Proliferation; Disease Models, Animal; DNA-Binding Proteins; Down-Regulation; Female; Fetal Death; Fetal Growth Retardation; Fetal Weight; Gestational Age; Glycogen; Hypothyroidism; Immunohistochemistry; Minichromosome Maintenance Complex Component 7; Neovascularization, Physiologic; Placenta; Pregnancy; Propylthiouracil; Rats; Trophoblasts; Vascular Endothelial Growth Factor A

Thyroid dysfunction can compromise physical capacity. Here, we analyze the effects of hyperthyroidism and hypothyroidism on maximum swim time in rats subjected to acute forced swimming, as an indicator of anaerobic capacity. Animals were forced to swim against a load (5% of body weight) attached to the tail and were killed 48 hours after the last test. Hyperthyroid rats were treated with thyroxine (50 mug/100 g body weight, i. p. for 7 days). The hypothyroid group received 0.03% methimazole in the drinking water for 4 weeks. Thyroid state was confirmed by alterations in serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and liver mitochondrial glycerol phosphate dehydrogenase (mGPD) activity. Hyperthyroid rats presented significantly lower visceral fat mass (VFM) and higher food intake (p<0.05) with unchanged body weight. Maximum swim time (MST), glycogen content (skeletal muscle and liver), and leptin levels were lower while corticosterone was higher (p<0.05). In hypothyroid rats body weight was lower (p<0.05), without changes in VFM. Tested at 7-day intervals, MST was lower for tests 2, 3, and 4 (p<0.05). Muscle glycogen was higher in extensor digitorum longus (EDL) and soleus (p<0.05), without changes in liver. Serum corticosterone was lower, while leptin was higher (p<0.05). These results suggest that in hyperthyroid and hypothyroid rats, thyroid hormones together with corticosterone and/or leptin may impair exercise capacity differently through its known effects on glycogen metabolism.

Topics: Animals; Body Composition; Corticosterone; Eating; Exercise Tolerance; Glycogen; Hyperthyroidism; Hypothyroidism; Leptin; Liver Glycogen; Male; Muscle, Skeletal; Rats; Rats, Wistar; Swimming; Thyrotropin; Thyroxine

An investigation was made to reveal the possible involvement of thyroid hormones in the progression of diabetes mellitus in response to an atherogenic diet; CCT (4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil). Following the intake of CCT diet for 14 consecutive days a decrease in the serum levels of insulin, both the thyroid hormones, triiodothyronine (T(3)) and thyroxine (T(4)); hepatic glycogen content, hepatic type-1 iodothyronine 5'-mono-deiodinase (5'D) and serum alpha-amylase activities were observed, while there was an increase in the levels of serum glucose and nitrite and in lipid peroxidation of heart, liver and kidney tissues as well as in serum. However, simultaneous administration of L-thyroxine (500 microg/kg/day, s.c.) to CCT-diet fed animals resulted in the amelioration of all the aforesaid adverse changes including that of serum glucose, insulin, alpha-amylase, hepatic glycogen content and nitrite levels, suggesting the involvement of thyroid hormones in the progression of CCT-diet induced diabetes mellitus.

Topics: alpha-Amylases; Animals; Cholesterol; Creatine Kinase, MB Form; Diabetes Mellitus; Diet, Atherogenic; Glycogen; Hypothyroidism; Insulin; Iodide Peroxidase; Kidney; Lipid Peroxidation; Liver; Male; Myocardium; Nitrites; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses.

Topics: Adaptation, Physiological; Amiodarone; Animals; Calcium-Transporting ATPases; Dronedarone; Eating; Glycogen; Heart; Heart Rate; Hypothyroidism; In Vitro Techniques; Isomerism; L-Lactate Dehydrogenase; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myosins; Rats; Rats, Wistar; Sarcoplasmic Reticulum; Thyroid Hormone Receptors alpha; Thyroid Hormones; Weight Gain

Maternal hypothyroidism impairs fetal growth in the rat, but the mechanisms by which this occurs are unknown. Since the fetus derives its glucose supply from the mother, and maternal thyroidectomy may disturb maternal and placental glucose metabolism, we postulated that maternal and/or placental glucose metabolic compromise may contribute to fetal growth retardation in hypothyroid dams. Feto-placental growth, tissue glycogen stores and glucose levels in sera and amniotic fluid were determined in rat dams partially thyroidectomized (TX) before pregnancy and in euthyroid controls. Fetal body weight at 16, 19 and 21 days gestation (d.g.) was related to pre-mating maternal serum total thyroxine (TT(4)) levels; permanent fetal growth retardation occurred in severely (TX(s); pre-mating maternal serum TT(4)

Topics: Amniotic Fluid; Analysis of Variance; Animals; Blood Glucose; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Glucose; Glycogen; Hypothyroidism; Liver; Placenta; Pregnancy; Pregnancy Complications; Rats; Rats, Sprague-Dawley; Regression Analysis; Thyroxine

Based on our observations of energy sparing in heat-acclimated (AC) rat hearts, we investigated whether changes in preischemic glycogen level, glycolytic rate, and plasma thyroxine level mediate cardioprotection induced in these hearts during ischemia-reperfusion insults. Control (C) (24 degrees C), AC (34 degrees C, 30 days), acclimated-euthyroid (34 degrees C + 3 ng/ml l-thyroxine), and control hypothyroid (24 degrees C + 0.02% 6-n-propyl-2-thiouracil) groups were studied. Preischemic glycogen was higher in AC than in C hearts [39.0 +/- 8.5 vs. 19.2 +/- 4.2 (SE) micromol glucose/g wet wt; P < 0.0006], and the lactate produced vs. glycogen level during total ischemia ((13)C-NMR spectroscopy) was markedly slower (AC: -0.82x, r = 0.98 vs. C: -4.7x, r = 0.9). Time to onset of ischemic contracture was lengthened, and the fraction of hearts experiencing ischemic contracture was lowered. Pulse pressure recovery was improved in AC compared with C animals before, but not after, absolute sodium iodoacetate-induced glycolysis inhibition. Acclimated-euthyroid hearts exhibited decreased ischemic tolerance, whereas induced hypothyroidism in C improved cardiotolerance. Thus higher preischemic glycogen and slowed glycolysis are associated with hypothyroidism and are likely important mediators of the improved ischemic tolerance exhibited by AC hearts.

Topics: Acclimatization; Animals; Carbon Isotopes; Glucose; Glycogen; Glycolysis; Hot Temperature; Hypothyroidism; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Physical Endurance; Rats; Thyroxine

Changes in thyroid status affect metabolism not only directly, but influence it also by alterations in insulin secretion and action. Despite several investigations, these effects are, however, poorly characterised or even controversial. The aim of the studies was to investigate the effect of hyperthyreosis (HT) and hypothyreosis (HPT) on insulin binding by rat liver membranes. Some metabolic parameters reflecting insulin and thyroid hormones action were also determined. HT and HPT were developed by daily administration for 3 weeks of thyroxine (T (4) ) and thiouracil (TU), respectively. Experimental hyperthyreosis and hypothyreosis caused deep changes in metabolism. The greatest alterations were observed in body and thyroid glands weight, blood triiodothyronine (T (3) ), T (4), glucose, and insulin levels, liver glycogen amount and number of insulin receptors. HT reflected in rats in slower rate of growth and in smaller thyroid glands weight. In comparison to controls, T (4) concentration in HT was almost doubled and it was reduced by about 30% in HPT. Also, T(3), insulin and glucose levels in HT were heightened. Simultaneously, binding of insulin to liver membranes was elevated in HT and reduced in HPT. In HT the number of high affinity insulin receptors (HAIRs) and low affinity insulin receptors (LAIRs) was increased, whereas in HPT the amount of HAIRs was diminished. HT caused a drastic reduction of glycogen concentration in liver, but no changes were observed for muscle glycogen. Considering lipid metabolism, only free fatty acids (FFA) level in blood was changed (in HPT), but no differences were observed in serum concentration of triglycerides and cholesterol. Several metabolic changes observed in HT and HPT seem to be the dire ct consequence of alterations of thyroid hormone concentrations. These disturbances, together with the direct effect of HT or HPT on insulin secretion, binding and action lead, in turn, to changes in the other metabolic parameters. As a result of these disturbances the adaptive mechanisms appear. One of them is change in the number of insulin membrane receptors taking place even against the well known "down-regulation" theory.

Topics: Animals; Antithyroid Agents; Cholesterol; Fatty Acids, Nonesterified; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Insulin; Liver; Male; Protein Binding; Rats; Rats, Wistar; Receptor, Insulin; Thiouracil; Thyroxine; Triglycerides

The effects of insulin on the rates of glucose disposal were studied in soleus muscles isolated from hyper- or hypothyroid rats. Treatment with triiodothyronine for 5 or 10 days decreased the sensitivity of glycogen synthesis but increased the sensitivity of lactate formation to insulin. The sensitivity of 3-O methylglucose to insulin was increased only after 10 days of treatment and was accompanied by an increase in the sensitivity of 2-deoxyglucose phosphorylation; however, 2-deoxyglucose and glucose 6-phosphate in response to insulin remained unaltered. In hypothyroidism, insulin-stimulated rates of 3-O-methylglucose transport and 2-deoxyglucose phosphorylation were decreased; however, at basal levels of insulin, 3-O-methylglucose transport was increased, while 2-deoxyglucose phosphorylation was normal. In these muscles, the sensitivity of lactate formation to insulin was decreased; this defect was improved after incubation of the muscles with prostaglandin E2. The results suggest: (a) in hyperthyroidism, insulin-stimulated rates of glucose utilization in muscle to form lactate are increased mainly because of a decrease in glycogen synthesis; when hyperthyroidism progresses in severity, increases in the sensitivity of glucose transport to insulin and in the activity of hexokinase may also be involved; (b) in hypothyroidism, the decrease in insulin-stimulated rates of glucose utilization is caused by decreased rates of glycolysis; (c) prostaglandins may be involved in the changes in sensitivity of glucose utilization to insulin observed in muscle in altered thyroid states.

Topics: Animals; Biological Transport, Active; Cortisone; Dinoprostone; Drug Interactions; Glucose; Glycogen; Glycolysis; Growth Hormone; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Insulin; Lactic Acid; Male; Muscle, Skeletal; Phosphorylation; Rats; Rats, Wistar; Triiodothyronine

The effects of alterations in thyroid status on glucose metabolism have been investigated in rat hepatocytes. Addition of 10 or 40 mmol/L glucose induced increases in respiration rate that were significantly larger in cells from hyperthyroid rats than from hypothyroid animals. The responses of hepatocytes from euthyroid rats were intermediate. In cells from hyperthyroid rats, most of the increase occurred upon addition of 10 mmol/L glucose, with only a further small stimulation resulting when glucose concentration was increased to 40 mmol/L. For a given glucose concentration, glycolytic rates, determined by measuring release of tritium from [6-3H]glucose, were comparable in all thyroid states. Studies with 10 mmol/L [2-3H]glucose showed that cycling between glucose-6-phosphate and glucose was almost twofold higher in euthyroid and hyperthyroid states as compared with the hypothyroid state, although the magnitude of the increase in cycling rate was only approximately 0.2 mumol glucose.min-1.g-1. When 40 mmol/L [2-3H]glucose was added, over 44% of the glucose that was phosphorylated to glucose-6-phosphate was cycled back to glucose, but this cycling was independent of thyroid status. Cycling between fructose-1,6-bisphosphate and fructose-6-phosphate was negligible in all thyroid states. Rates of glycogen synthesis were comparable in hypothyroid and hyperthyroid states and slightly less than in the euthyroid state. Glycolytically formed pyruvate was cycled back to glucose in hepatocytes from hypothyroid, euthyroid, and hyperthyroid rats. During a 60-minute incubation period, cycling to glucose in the presence of 10 mmol/L or 40 mmol/L glucose was up to twofold higher in cells from euthyroid and hyperthyroid rats than in hepatocytes from hypothyroid animals. The measured increases in cycling rates induced by thyroid hormone were small and in theory could have been satisfied by a much smaller increase in respiration rate than was observed.

Topics: Animals; Dose-Response Relationship, Drug; Fructosediphosphates; Fructosephosphates; Glucose; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Hyperthyroidism; Hypothyroidism; Lactates; Liver; Oxidation-Reduction; Oxygen Consumption; Phosphorylation; Pyruvates; Pyruvic Acid; Rats; Thyroid Gland; Tritium

Female rats were mated and thyroidectomized on the same day. Some animals were kept without treatment and killed on day 12 or 21 of gestation (T). Others were subsequently treated daily with 1.8 micrograms L-T4/100 g BW for either the first 12 days and then not treated from that time until day 21 [T+T4(I+0)] or else not treated for the first 12 days and then treated from days 12-21 [T+T4(0+II)]. A final group received treatment during the entire 21-day study [T+T4(I+II)] and was used as the control. The net maternal body weight increased until day 12 of gestation in T+T4(I+II) rats, but not in T animals. On day 21 net maternal body weight was significantly lower in T and T+T4(0+II) than in T+T4(I+II) rats. Lipoprotein lipase activity in the lumbar fat pads increased from days 0 to 12 of gestation and decreased on day 21, whereas in the heart the change was in the opposite direction, and these changes were greater in T+T4(I+II) rats than in T rats. Incorporation of [U-14C]glucose administered in vivo into liver [14C]fatty acids or [14C]glycogen was significantly lower in T rats than in T+T4(I+II) on either the 12th or 21st day of gestation. The response of plasma triglyceride, glycerol, or beta-hydroxybutyrate levels to 24 h of starvation was similar in 12-day pregnant rats regardless of whether they were treated with T4, whereas on day 21 the change was greater in T+T4(I+II) or T+T4(I+0) animals than in T or T+T4(0+II) animals. Results show that maternal hypothyroidism during the first half of gestation impaired the anabolic events occurring during this phase and compromised the normal catabolic response during late gestation even when T4 treatment was restored. However, once maternal metabolic stores were built up normally during the first half of gestation, maternal hypothyroidism during late gestation did not affect the mother's normal metabolic adaptation, including the accelerated response to starvation.

Topics: Adipose Tissue; Animals; Blood Glucose; Fatty Acids; Female; Glucose; Glycogen; Hypothyroidism; Insulin; Lipoprotein Lipase; Liver; Myocardium; Pregnancy; Pregnancy Complications; Rats; Rats, Inbred Strains; Starvation; Thyrotropin; Thyroxine; Time Factors; Weight Gain

Topics: Animals; Glycogen; Hypothyroidism; Organ of Corti; Rats

A 28-year-old man on thyroid hormone replacement following treatment with radioactive iodine for Graves' disease developed an episode of acute exertional rhabdomyolysis. He was found to be hypothyroid and had no rise in serum lactic acid following an ischemic exercise test. With additional thyroid replacement, his ischemic exercise test normalized and his muscle symptoms resolved. This observation suggests that rhabdomyolysis in hypothyroidism may be due to a reversible defect in glycogenolysis and that hypothyroidism should be excluded in patients with rhabdomyolysis and/or myoglobinuria.

Topics: Adult; Exercise Test; Glycogen; Humans; Hypothyroidism; Male; Physical Exertion; Rhabdomyolysis

The density of glycogen particles in organ of Corti's sensory cells was measured to determine the effect of congenital hypothyroidism upon the normal development of this energy source. This density in both normal and hypothyroid inner hair cells remains in low values from birth to adulthood. On the other hand, that of normal outer hair cells undergoes a great increase between the 10th and the 20th postnatal days, coinciding with the maturation of both the efferent innervation of these cells and the tuning properties of the auditory receptor. The glycogen stores of the hypothyroid outer hair cells do not show any significant increase from birth to adulthood. This latter fact suggests that the congenital hypothyroidism restrains the development of an important energy source of outer hair cells, most surely disturbing the physiological processes relying on glycogen metabolism.

Topics: Animals; Glycogen; Hypothyroidism; Organ of Corti; Rats; Thyroid Hormones

The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates.

Topics: Animals; Animals, Newborn; Body Weight; Female; Fetal Heart; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Lipid Metabolism; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Proteins; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroxine

1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations.

Topics: Animals; Dose-Response Relationship, Drug; Glycogen; Glycolysis; Hypothyroidism; In Vitro Techniques; Insulin; Male; Muscles; Oxidation-Reduction; Phosphorylation; Rats; Rats, Inbred Strains

1. The effects of hypothyroidism (caused by surgical thyroidectomy followed by treatment for 1 month with propylthiouracil) and of hyperthyroidism [induced by subcutaneous administration of L-tri-iodothyronine (T3)] on glucose tolerance and skeletal-muscle sensitivity to insulin were examined in rats. Glucose tolerance was estimated during 2 h after subcutaneous glucose injection (1 g/kg body wt.). The sensitivity of the soleus muscle to insulin was studied in vitro in sedentary and acutely exercised animals. 2. Glucose tolerance was impaired in both hypothyroid and hyperthyroid rats in comparison with euthyroid controls. 3. In the soleus muscle, responsiveness of the rate of lactate formation to insulin was abolished in hypothyroid rats, whereas the sensitivity of the rate of glycogen synthesis to insulin was unchanged. In hyperthyroid animals, opposite changes were found, i.e. responsiveness of the rate of glycogen synthesis was inhibited and the sensitivity of the rate of lactate production did not differ from that in control sedentary rats. 4. A single bout of exercise for 30 min potentiated the stimulatory effect of insulin on lactate formation in hyperthyroid rats and on glycogen synthesis in hypothyroid animals. 5. The data suggest that thyroid hormones exert an interactive effect with insulin in skeletal muscle. This is likely to be at the post-receptor level, inhibiting the effect of insulin on glycogen synthesis and stimulating oxidative glucose utilization.

Topics: Animals; Glucose Tolerance Test; Glycogen; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Insulin; Lactates; Male; Muscles; Physical Conditioning, Animal; Rats; Rats, Inbred Strains; Thyroid Hormones

A fraction containing a protein-glycogen complex was isolated from rat skeletal muscle in order to study the effect of hypothyroidism on phosphorylase activation in this structural and functional unit of the glycogenolytic process. The total activities of phosphorylase and phosphorylase phosphatase in euthyroids and hypothyroids were the same in the fraction containing the protein-glycogen complex (P2 suspension). Hypothyroidism selectively lowered the maximal phosphorylase kinase activity in glycogen particles in the P2 suspension by 40%. Addition of Mg2+ (10 mM), ATP (2 mM), and Ca2+ (5 mM) rapidly stimulated phosphorylase b to a conversion resulting from phosphorylase kinase activation. Hypothyroidism reduced the rate of phosphorylase a formation by 50-70% in the P2 suspension. Glucose 6-phosphate (0.4-1.4 mM) inhibited the rate of phosphorylase a formation and this inhibition was similar for eu- and hypothyroids. There was a shift from 5.2 to 5.8 in the free Ca2+ concentration (pCaF) for half-maximal activation of phosphorylase in the P2 suspension of hypothyroids. A sixfold higher steady-state level of phosphorylase in euthyroids compared to hypothyroids was observed at a pCaF of 5.5. The Ca2+ sensitivity of the phosphorylase kinase, however, was not changed by hypothyroidism. These results provide further insight into the different time course of the phosphorylase activation in skeletal muscle during tetanic stimulation observed in euthyroidism and hypothyroidism (W. J. Leijendekker et al. (1985) Metabolism 34, 437-441).

Topics: Animals; Calcium; Enzyme Activation; Glycogen; Hypothyroidism; Kinetics; Magnesium; Male; Muscles; Phosphorylase a; Phosphorylase Kinase; Phosphorylase Phosphatase; Phosphorylases; Proteins; Rats; Rats, Inbred Strains; Reference Values; Thyroid Gland

Isolated hepatocytes from hyperthyroid and euthyroid rats showed the same rate and extent of activation of glycogen synthase after addition of glucose (10 mM or 60 mM). In liver cells from hypothyroid rats this activation occurred at a 7-fold lower rate. However, complete activation of glycogen synthase occurred eventually in broken-cell preparations from either source during incubation in vitro. Glycogen synthase phosphatase was then quantitatively assayed in liver homogenates with exogenous synthase b as substrate. These assays revealed an increased synthase phosphatase activity (approximately 160%) in the hyperthyroid liver and a decreased activity (to approximately 60%) in the livers from hypothyroid rats. These activity changes involved both the cytosolic and the glycogen-bound synthase phosphatase. The increase in the activity of synthase phosphatase after the administration of T3 became maximal after 48 h. We conclude that thyroid hormones control hepatic glycogen synthesis, at least partly by an effect on synthase phosphatase.

Topics: Animals; Enzyme Activation; Glucose; Glycogen; Glycogen Synthase; Glycogen-Synthase-D Phosphatase; Hyperthyroidism; Hypothyroidism; Liver; Male; Phosphorylase a; Rats; Rats, Inbred Strains; Triiodothyronine

Crystalloid bodies in skeletal muscle fibers have been described in myopathic and non-myopathic conditions. They have been interpreted as viral, glycogen, protein-glycogen complex, artifacts and of unknown nature. This report described similar crystalloid bodies in the postmortem muscle samples of two patients with hypothyroid myopathy. The crystalloid bodies were preferentially located in the I band and Z line region and in the subsarcolemmal region closely associated with lipofuscin. Some were present within basophilic bodies. They were formed by parallel filaments of 6-10 nm beaded periodically by electron-dense particles of 10-18 nm in a lattice, hexagonal or parallel-ripple pattern. Merging of filaments of crystalloid bodies into actin filaments of the I band was noted. The electron-dense particles stained strongly with periodic acid-thiocarbohydrazide-silver proteinate method for polysaccharides and were unaffected or partially digested by diastase treatment on the ultrathin sections. The filamentous component was neither stained for polysaccharides nor digested by diastase treatment. It is suggested that crystalloid bodies of muscle fibers are composed of two distinct subunits with particles of glycogen complex attached to filaments of unknown nature.

Topics: Amylases; Crystallization; Female; Glycogen; Histocytochemistry; Humans; Hypothyroidism; Inclusion Bodies; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Polysaccharides

We investigated the effect of hyperthyroidism and hypothyroidism on the myocardial glycogen metabolism by quantitating 125I-insulin binding, glycogen content, glycogen synthase and phosphorylase enzyme activities in the newborn rabbit. Although an increase in 125I-insulin binding was observed in response to hyperthyroidism (p less than 0.01), a decrease in myocardial glycogen (p less than 0.01) along with no change in the synthase and phosphorylase enzyme activity was demonstrated. On the other hand, propylthiouracil-induced hypothyroxinemia did not affect the 125I-insulin binding, glycogen content or the two enzyme systems. We conclude that the depletion of myocardial glycogen secondary to hyperthyroidism is independent of an increase in 125I-insulin binding or any change in the major glycogen enzyme activities (synthase and phosphorylase). We speculate that this decline in neonatal heart glycogen may be secondary to thyroxine-induced altered glucose uptake or modified postinsulin receptor events.

Topics: Animals; Animals, Newborn; Blood Glucose; Congenital Hypothyroidism; Female; Fetal Diseases; Glycogen; Hyperthyroidism; Hypothyroidism; Insulin; Myocardium; Pregnancy; Rabbits; Thyroid Hormones; Thyroxine

The effects of hypothyroidism on glycogen metabolism in rat skeletal muscle were studied using the perfused rat hindlimb preparation. Three weeks after propylthiouracil treatment, serum thyroxine was undetectable and muscle glycogen and Glc-6-P were decreased. Basal and epinephrine-stimulated phosphorylase a and phosphorylase b kinase activities were also significantly reduced, as were epinephrine-stimulated cAMP accumulation and cAMP-dependent protein kinase activity. Conversely, basal and epinephrine-stimulated glycogen synthase I activities were significantly higher while the Ka of the enzyme for Glc-6-P was lower in hypothyroid animals. Propylthiouracil-treated rats also had increased phosphoprotein phosphatase activities towards phosphorylase and glycogen synthase and decreased activity of phosphatase inhibitor 1. beta-Adrenergic receptor binding and basal and epinephrine-stimulated adenylate cyclase activities were reduced in muscle particulate fractions from hypothyroid rats. Administration of triiodothyronine to rats for 3 days after 3 weeks of propylthiouracil treatment restored the altered metabolic parameters to normal. It is proposed that the decreased beta-adrenergic responsiveness of the enzymes of glycogen metabolism in hypothyroid rat skeletal muscle is due to increased activity of phosphoprotein phosphatases and to reduced beta-adrenergic receptors and adenylate cyclase activity.

Topics: Animals; Epinephrine; Glycogen; Hypothyroidism; Kinetics; Male; Muscles; Phosphorylase Kinase; Phosphorylases; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Thyroxine; Triiodothyronine

The relation between Ca2+ efflux, Ca2+ mobilization from mitochondria and glycogenolysis was studied in perfused euthyroid and hypothyroid rat livers stimulated by Ca2+-mobilizing hormones. Ca2+ efflux, induced by noradrenaline (1 microM) in the absence or presence of DL-propranolol (10 microM) from livers perfused with medium containing a low concentration of Ca2+ (approx. 24 microM), was decreased by more than 50% in hypothyroidism. This correlated with an equal decrease of the fractional mobilization of mitochondrial Ca2+, which could account for 65% of the difference between the net amounts of Ca2+ expelled from the euthyroid and hypothyroid livers. With vasopressin (10 nM) similar results were found, suggesting that hypothyroidism has a general effect on mobilization of internal Ca2+. In normal Ca2+ medium (1300 microM), however, the effect of vasopressin on net Ca2+ fluxes and phosphorylase activation was not impaired in hypothyroidism, indicating that Ca2+ mobilization from the mitochondria in this case plays a minor role in phosphorylase activation. The alpha 1-adrenergic responses of Ca2+ efflux, phosphorylase activation and glucose output, glucose-6-phosphatase activity and oxygen consumption in hypothyroid rat liver were completely restored by in vivo T3 injections (0.5 micrograms per 100 g body weight, daily during 3 days). Perfusion with T3 (100 pM) during 19 min did not influence hypothyroid rat liver oxygen consumption and alpha 1-receptor-mediated Ca2+ efflux. However, this in vitro T3 treatment showed a completely recovered alpha 1-adrenergic response of phosphorylase and a partly restored glucose-6-phosphatase activity and glucose output. The results indicate that thyroid hormones may control alpha 1-adrenergic stimulation of glycogenolysis by at least two mechanisms, i.e., a long-term action on Ca2+ mobilization, and a short-term action on separate stages of the glycogenolytic process.

Topics: Animals; Calcium; Calcium Chloride; Glucose; Glucose-6-Phosphatase; Glycogen; Hypothyroidism; Liver; Male; Mitochondria, Liver; Norepinephrine; Propranolol; Rats; Rats, Inbred Strains; Thyroid Hormones; Thyroidectomy; Triiodothyronine; Vasopressins

Glucose metabolism was studied as evidenced by the sugar and pyruvic acid levels in blood and glycogen and pyruvic acid content of tissues in euthyroid, hypothyroid and hyperthyroid rats by giving insulin. Results show that in a normal thyroxine-excess insulin state, the rise in blood sugar was less, glycogenesis was much enhanced and glycolysis was reduced in comparison to these data in the euthyroid state. When tyroxine deficiency was associated with excess insulin, glycogenesis was enhanced further and an almost complete inhibition of glycolysis was observed. In excess thyroxine-excess insulin state glycogenesis was increased at the expense of glycolysis in comparison to the finding in the hyperthyroid state. Thus exogenous insulin in the euthyroid state altered the pattern of carbohydrate metabolism enhancing glycogenesis and inhibiting glycolysis. In a low thyroxine-excess insulin state, further enhancement of glycogenesis and inhibition of glycolysis were observed. But in an excess thyroxine-excess insulin state, the higher thyroxine activity was somewhat neutralized by higher insulin action allowing glycogenesis with glucose to proceed to some extent.

Topics: Animals; Blood Glucose; Female; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Insulin; Kidney; Liver; Liver Glycogen; Male; Myocardium; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains; Thyroxine

The effect of gestational hypothyroidism on some maternal and foetal metabolites were studied on pregnant rats after 24 h fasting. Thyroidectomy induced a decrease in body weight in the pregnant rats. Their foetuses showed lower weights than the controls. No difference was found in circulating glucose levels in the thyroidectomized pregnant rats, although an increase was found in their foetuses. Hepatic glycogen and total serum lipids decrease in hypothyroid pregnant rats. Cholesterol concentration increases as a result of hypothyroidism. However, foetuses coming from thyroidectomized mothers show an increase in their total lipid levels. Hypothyroidism in pregnant rats affects foetal development and metabolic changes are greatly manifested in the starved condition.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol; Female; Fetal Blood; Glycogen; Hypothyroidism; Lipids; Liver; Pregnancy; Pregnancy Complications; Rats; Rats, Inbred Strains

The actions of hormones which are associated to cAMP-dependent and calcium-dependent mechanisms of signal transduction were studied in hepatocytes obtained from rats with different thyroid states. In cells from euthyroid and hyperthyroid rats, the metabolic actions of epinephrine were mediated mainly through alpha 1-adrenoceptors; beta-adrenoceptors seem to be functionally unimportant. In contrast, both alpha 1- and beta-adrenoceptors mediate the actions of epinephrine in hepatocytes from hypothyroid animals. Phosphatidylinositol labeling was strongly stimulated by epinephrine, vasopressin and angiotensin II in cells from eu-, hyper- or hypothyroid rats. However, metabolic responsiveness to vasopressin and angiotensin II was markedly impaired in the hypothyroid state. The glycogenolytic response to the calcium ionophore A-23187 was also impaired, suggesting that hepatocytes from hypothyroid rats are less sensitive to calcium signalling. The persistence of alpha 1-adrenergic responsiveness in the hypothyroid state suggests that the mechanism of signal transduction for alpha 1-adrenergic amines is not identical to that of the vasopressor peptides. alpha 1-Adrenergic stimulation of cyclic AMP accumulation was not detected in cells from hypothyroid rats. These data suggest that factors besides calcium and besides cAMP are probably involved in alpha 1-adrenergic actions. Metabolic responses to glucagon and to the cAMP analogue dibutyryl cAMP were not markedly changed during hypothyroidism, although cAMP accumulation produced by glucagon and beta-adrenergic agonists was enhanced. In hyperthyroidism, cell responsiveness to epinephrine, vasopressin, angiotensin II and glucagon was decreased, but sensitivity to cAMP was not markedly altered. The factors involved in this hyposensitivity to hormones during hyperthyroidism are unclear.

Topics: Angiotensin II; Animals; Calcium; Cyclic AMP; Gluconeogenesis; Glycogen; Hyperthyroidism; Hypothyroidism; Liver; Liver Glycogen; Phosphatidylinositols; Rats; Receptors, Adrenergic, alpha; Urea; Vasopressins

Topics: Acid Phosphatase; Adult; Female; Glucuronidase; Glycogen; Humans; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Leukocyte Count; Male; Middle Aged; Neutrophils; Oxidation-Reduction; Oxidoreductases; Phagocytosis

Changes induced in liver and striated muscle glycogen and glycogen enzymes (glycogen synthetase, glycogen phosphorylase and alpha-amylase) by hypothyroidism and hyperthyroidism in rats have been determined. There were no changes in liver glycogen synthetase, phosphorylase and amylase activities in the hypothyroid group. Hyperthyroid rats showed lower liver glycogen synthetase, phosphorylase a and amylase activities. In muscle, hypothyroid rats had lower phosphorylase activity. In the hyperthyroid group glycogen synthetase was increased.--The results presented do not completely agree with the glycogen levels found in both tissues studied, and they are obviously more related to other factors such as glucose availability. It can be concluded that under the conditions studied, the glycogen enzyme levels could not alone explain the variations of glycogen levels.

Topics: Amylases; Animals; Blood Glucose; Body Weight; Glycogen; Glycogen Synthase; Hyperthyroidism; Hypothyroidism; Liver; Liver Glycogen; Male; Muscles; Phosphorylases; Rats; Rats, Inbred Strains

1. The role of endogenous glucagon and insulin on the hypolipidemic and glycogenolytic effect of clofibrate was determined in the euthyroid and propylthiouracil (PTU)-induced hypothyroid mice. 2. PTU was fed in diet (0.15%) for 2 weeks and then clofibrate added to diet (0.25%) for 4 weeks. 3. Both PTU and clofibrate significantly increased liver weight but had no effect on kidney weight. PTU significantly decreased plasma triglycerides (TG) and increased cholesterol (Ch). 4. Clofibrate had a significant hypotriglyceridemic effect in both euthyroid and hypothyroid mice but did not affect plasma cholesterol. 5. Clofibrate decreased hepatic glycogen in euthyroid but not in hypothyroid mice. 6. Glucose-6-phosphatase activity was not affected by either PTU or clofibrate. 7. Neither PTU nor clofibrate affected hepatic TG or Ch. 8. Biliary lipid changes due to PTU treatment were reversed by clofibrate administration. 9. Since plasma insulin and glucagon levels were not affected by clofibrate in either euthyroid or hypothyroid mice, our results suggest that the hypotriglyceridemic and glycogenolytic effect of clofibrate is not mediated by changes in circulating insulin and glucagon ratio. 10. Moreover, while the glycogenolytic effect of clofibrate seems to be dependent, the hypotriglyceridemic effect seems to be independent of thyroid hormones.

Topics: Animals; Clofibrate; Glucagon; Glycogen; Hypolipidemic Agents; Hypothyroidism; Insulin; Lipid Metabolism; Liver Glycogen; Male; Mice; Organ Size; Propylthiouracil

The role of endogenous glucagon and insulin on the hepatic glycogen and triglyceride storage syndrome in propylthiouracil (PTU)-induced hypothyroidism was investigated in the chick. PTU feeding in the diet resulted in a progressive increase in liver glycogen concentration associated with a concomitant decrease in hepatic glucose-6-phosphatase (G-6-Pase) activity. Plasma glucagon level was significantly decreased and insulin significantly increased after two days of PTU administration. These enzyme and hormone changes were associated with a significant increase in hepatic glucose-6-phosphate (G-6-P) and a decrease in cyclic AMP levels. Although our results do not directly prove, the data does suggest that the hepatic glycogen storage syndrome observed in the PTU-induced hypothyroidism in the chick is mediated through changes in pancreatic glucagon and insulin secretion. The extent of glycogen accumulation was inversely related to G-6-Pase which is a rate limiting glycogenolytic enzyme. A significant increase in the plasma insulin/glucagon ratio, along with a significant decrease in the hepatic cyclic AMP concentration, could most likely also account for the excessive hepatic triglyceride accumulation in the PTU-treated chicks.

Topics: Animals; Blood Glucose; Chickens; Cholesterol; Cyclic AMP; Glucagon; Glucose-6-Phosphatase; Glycogen; Hypothyroidism; Insulin; Liver; Male; Phospholipids; Propylthiouracil; Triglycerides

This study was undertaken to determine the effects of propylthiouracil-induced thyroid deficiency on a) the capacity of muscle homogenates to oxidize [2-14C]pyruvate and [U-14C]palmitate and b) glycogen depletion during exercise in liver and in fast-oxidative-glycogenolytic (FOG), fast-glycogenolytic (FG), and slow-oxidative (SO) muscle. Relative to the rates for normal rats, oxidation with pyruvate was reduced by 53, 68, and 58%, and palmitate by 40, 50, and 48% in FOG, FG, and SO muscle, respectively (P less than 0.05). Normal rats ran longer than thyroid-deficient rats at 26.7 m/min (87 +/- 8 vs. 37 +/- 5 min). After 40 min of running (22 m/min), the amount of glycogen consumed in normal FOG, FG, and SO muscle and in liver amounted to only 23, 12, 66, and 52%, respectively, of that for their thyroid-deficient counterparts. Also, normal rats maintained higher plasma free fatty acid levels than thyroid-deficient rats during both rest and exercise (P less than 0.05). These findings suggest that thyroid deficiency causes a reduced potential for FFA utilization in skeletal muscle that enhances its consumption of glycogen, thereby limiting endurance capacity.

Topics: Animals; Blood Glucose; Citrate (si)-Synthase; Fatty Acids, Nonesterified; Female; Glycogen; Hexokinase; Hypothyroidism; Malate Dehydrogenase; Muscles; Physical Exertion; Propylthiouracil; Rats; Respiration

Topics: Adenosine Triphosphate; Animals; Creatine; Creatine Kinase; Glycogen; Hyperthyroidism; Hypothyroidism; Muscles; Phosphocreatine; Rats

Electron microscopic studies of the liver of thyroidectomized rabbits were carried out. Ultrastructural changes in hepatocytes at various periods after the operation were established. Morphological changes in hepatic cells occurred already at early stages of hypothyrosis (1 month) and led to considerable dystrophyc processes at later stages of the experiment. In the hepatic tissue there was noted a marked myxedema, as well as a considerable intracellular edema which led to destruction of hepatocytes. The studies conducted revealed lesion of the morphological structure of the liver, impairment of general metabolic processes and of the hepatic function.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cytoplasm; Glucose-6-Phosphatase; Glycogen; Hypothyroidism; Lipids; Liver; Microscopy, Electron; Mitochondria, Liver; Rabbits; Succinate Dehydrogenase

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%-0.86% (normal 1.06%), but reduced activity of acid maltase, 32-50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.

Topics: Adolescent; Adult; Alanine; Blood Glucose; Creatine Kinase; Fatty Acids, Nonesterified; Female; Glycogen; Humans; Hypothyroidism; Ischemia; Lactates; Male; Middle Aged; Muscles; Muscular Diseases; Reference Values; Thyrotropin

Topics: Fructose-1,6-Diphosphatase Deficiency; Galactose; Gluconeogenesis; Glucosephosphate Dehydrogenase Deficiency; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Humans; Hyperinsulinism; Hypoglycemia; Hypothyroidism; Insulin; Lactates; Leucine; Parathyroid Hormone; Phosphorylases; Pyruvate Carboxylase Deficiency Disease

Maternal hypothyroidism in rats has been shown previously to result in alterations of maternal, placental, and fetal metabolism. Maternal treatment with 2 IU GH/day for three days prior to autopsy (on the 22nd day of pregnancy) corrected many of the observed alterations of carbohydrate metabolism in hypothyroidism. The maternal and fetal liver glycogen concentrations and the fetal serum glucose levels of the hypothyroid animals were elevated significantly by the GH treatment. In most cases, the utilization of a [1-14C]glucose tracer dose was returned to normal by GH treatment. These results suggest that the impairment of fetal metabolism occurring in maternal hypothyroidism may be due in part to insufficient maternal GH secretion. However, GH alone in the absence of sufficient thyroid hormones did not totally correct all of the observed fetal abnormalities.

Topics: Animals; Blood Glucose; Body Weight; Female; Fetus; Glucose; Glycogen; Growth Hormone; Hypothyroidism; Liver; Liver Glycogen; Maternal-Fetal Exchange; Muscles; Organ Size; Parathyroid Glands; Placenta; Pregnancy; Rats; Thyroidectomy

Thyroid hormoned influence the quantitative cytoarchitecture of hepatocytes by stimulating the membrane synthesis of mitochondria and ergastoplasm. The cellular and nuclear changes produced by thyroidectomy were analysed cytophotometrically and morphometrically.. 21 days after thyroidectomy the liver tissues of 10 male Wistar rats were examined. 5 sham-operated animals served as controls. All rats received Altromin-R-standard diet. The cytophotometric analysis is based on the method described by Sandritter. The morphometric study was carried out following Weibel's methods.. As a consequence of the changed cellular metabolism, smaller hepatocytes and nuclei (but larger nucleoli) are found in the hypothyroid rats. As compared with controls, hepatocytes hardly show tetraploid nuclei, which is due to inhibited polyploidisation. The mitochondrial content has become considerably smaller in the hypothyroid hepatocytes. The cristal membranes, the mitochondrial and peroxysomal volume per hepatocyte show a similar reaction pattern, which is considered to be a sign of reduced cellular metabolism. The volume loss of the ergastoplasm confirms this assumption.

Topics: Animals; Biometry; Cell Nucleus; Cytological Techniques; Diploidy; Endoplasmic Reticulum; Glycogen; Hypothyroidism; Karyometry; Liver; Lysosomes; Male; Membranes; Mitochondria, Liver; Organoids; Photometry; Polyploidy; Rats; Thyroid Hormones; Thyroidectomy

Maternal hypothyroidism, when induced by surgical thyroidectomy with parathyroid hormone replacement, results in fewer live fetuses and smaller fetuses at the 22nd day of gestation. The hypothyroid mother shows the ability to mobilize adequate amounts of glucose even at the expense of her own reserves but the supply of glucose to the fetus appears to be impaired. These fetuses have subnormal skeletal muscle and liver glycogen and are severely hypoglycemic. The impaired development of these fetuses may result from alterations of either transplacental carbohydrate transport or placentofetal carbohydrate metabolism.

Topics: Animals; Blood Glucose; Calcium; Female; Fetal Blood; Fetal Diseases; Fetus; Glycogen; Hypoglycemia; Hypothyroidism; Litter Size; Liver; Liver Glycogen; Maternal-Fetal Exchange; Organ Size; Parathyroid Glands; Parathyroid Hormone; Pregnancy; Pregnancy Complications; Rats; Thyroidectomy

These experiments were conducted to help elucidate the mechanism for the impaired fetal development occurring during maternal hypothyroidism. The disposition of glucose was measured using glucose-1-14C. Maternal hypothyroidism depressed glucose utilization in thematernal-fetal system. Maternal net glycogen synthesis from the labeled glucose was impaired. However, while the fetal glycogen storage system may be capable of at least relatively normal glycogen synthesis, abnormally low levels of glycogen were measured. If, as the data suggest, enzymatic deficiencies do not exist, the low liver glycogen might be a result of the inability of the maternal-placental system to provide adequate substrate to the fetus.

Topics: Animals; Blood Glucose; Female; Fetus; Glucose; Glycogen; Hypothyroidism; Liver; Liver Glycogen; Maternal-Fetal Exchange; Muscles; Organ Specificity; Placenta; Pregnancy; Pregnancy Complications; Rats; Thyroidectomy

Topics: Adenosine Triphosphate; Amino Acids; Animals; Body Weight; Brain; Brain Chemistry; Carbon Dioxide; Carbon Radioisotopes; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Leucine; Lipids; Liver; Organ Size; Phosphocreatine; Rats; Time Factors

Topics: Action Potentials; Child; Child, Preschool; Congenital Hypothyroidism; Creatine Kinase; Electromyography; Female; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Hypertrophy; Hypothyroidism; L-Lactate Dehydrogenase; Lipid Metabolism; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Neuromuscular Junction; Sarcoplasmic Reticulum; Syndrome; Thyroxine

Topics: Alanine; Animals; Antigens; Biological Transport; Blood Glucose; Body Weight; Carbon Radioisotopes; Chromatography, Paper; DNA; Fasting; Female; Gluconeogenesis; Glucose; Glycogen; Hypothyroidism; Insulin; Ketone Bodies; Lactates; Liver; Organ Size; Radioimmunoassay; Rats; Thyroid Function Tests; Thyroid Gland; Thyroidectomy; Time Factors

Topics: Acyltransferases; Adolescent; Adult; Alkaline Phosphatase; Anemia, Hemolytic; Biliary Tract Diseases; Child; Child, Preschool; Cystic Fibrosis; Erythroblastosis, Fetal; Female; gamma-Glutamyltransferase; Glutamate Dehydrogenase; Glycogen; Hematologic Diseases; Hepatitis A; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Kidney Diseases; Leucyl Aminopeptidase; Neoplasms; Oxidoreductases; Pregnancy

Topics: Child, Preschool; Congenital Hypothyroidism; Glycogen; Histocytochemistry; Humans; Hypertrophy; Hypothyroidism; Male; Muscles; Muscular Diseases

Topics: Adolescent; Adult; Age Factors; Aged; Cardiomyopathies; Child; Child, Preschool; Cytoplasm; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Hypothyroidism; Infant; Infant, Newborn; Microscopy, Electron; Middle Aged; Myocardium; Myoclonus; Polysaccharides; Staining and Labeling

Topics: Action Potentials; Aged; Biopsy; Demyelinating Diseases; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hypothyroidism; Male; Microscopy, Electron; Middle Aged; Neural Conduction; Peripheral Nerves; Polyneuropathies; Thyroid Hormones

Topics: Adolescent; Adult; Alkaline Phosphatase; Blood Cells; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Chile; Female; Glycogen; Histocytochemistry; Humans; Hypothyroidism; Infant; Lipid Metabolism; Male

Topics: Animals; Dactinomycin; Glucosyltransferases; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Glycolysis; Hexokinase; Hydro-Lyases; Hypothyroidism; Iodine Isotopes; Isomerases; Male; Muscles; Nucleotidyltransferases; Phosphoglucomutase; Phosphoglycerate Kinase; Phosphopyruvate Hydratase; Phosphotransferases; Rats; Stimulation, Chemical; Triiodothyronine

Topics: Animals; Glucosyltransferases; Glycogen; Hypothyroidism; Muscles; Phosphoric Monoester Hydrolases; Phosphorylase Kinase; Rats; Thyroid Gland; Thyroxine

Topics: Animals; Carbon Isotopes; Gluconeogenesis; Glycogen; Glycolysis; Hypothyroidism; Liver; Male; Propylthiouracil; Rats

Topics: Animals; Glycogen; Hypothyroidism; Liver; Rats; Testosterone; Testosterone Propionate