vasoactive-intestinal-peptide and Hypothyroidism

Effects of primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of GnRH to HYPO rats and humans may increase or decrease gonadotropin secretion. Since inhibitory effects of HYPO on the GnRH-gonadotropin axis are reversed by replacement with L-T4, it has been suggested that thyroid hormone (TH) may regulate tuberoinfundibular GnRH and pituitary gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic GnRH neurons, LH, PRL and vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when GnRH biosynthesis is reduced by HYPO, gonadotropin secretion may be rescued by local activating effects of VIP. Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether central hypothyroidism may contribute to the pathophysiology of PCB-induced hypogonadism. On the basis of preliminary animal data, we speculate that one of the mechanisms for Partial Androgen Deficiency of the Aging Male may involve central hypothyroidism and EDD-NTIS, resulting in inhibition of the GnRH-gonadotroph axis.

Topics: Animals; Autocrine Communication; Endocrine Disruptors; Euthyroid Sick Syndromes; Gonadotropin-Releasing Hormone; Gonadotropins; Gonads; Hypothyroidism; Luteinizing Hormone; Male; Models, Biological; Neurons; Paracrine Communication; Prolactin; Rats; Thyroid Hormones; Vasoactive Intestinal Peptide

Heat stress (HS) effects on reproductive and thyroid hormones have been well documented; however, mechanisms of action are not well understood. Two studies were conducted to determine whether HS-induced and hypothyroid-induced effects are similar in the laying hen, with regard to reproductive hormones and vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the hypothalamus. In study 1, thirty 32-wk-old Hy-Line W-36 laying hens, housed at 22 degrees C, were cannulated. On d 0 and then on d 1 to 5 of HS (35 degrees C, 50% RH), a daily blood sample was obtained and assayed for triiodothyronine (T(3)), thyroxine (T(4)), 17beta-estradiol (E(2)), progesterone (P(4)), prolactin (PRL), and VIP, and T(3):T(4)was calculated. On d 0, 1, 3, and 5, livers were obtained for hepatic type I deiodinase mRNA (cDI-1) determination. In study 2, eighty 32-wk-old hens were randomly assigned to 4 treatments of 20 birds each: 1) HS (36.5 degrees C, 50% RH), 2) thiouracil-induced hypothyroidism (HY), 3) HY + T(4) administration, and 4) control (22 degrees C). Beginning on d 1 of the 5-d study, daily blood samples (3.0 mL) were removed and assayed as in study 1. On d 5, brains were removed from 3 hens/treatment and immunoreactivity of VIP cells was determined. In study 1, HS reduced E(2), P(4), T(3) (P = 0.0001), T(3):T(4) ratio (P = 0.0078), and hepatic type I deiodinase mRNA (P = 0.0204) and increased T(4) (P = 0.0013); there was no effect on VIP or PRL. In study 2, HS and HY reduced T(3), T(3):T(4) ratio, and E(2) (P = 0.0001) and increased PRL (P = 0.0045); HS alone decreased P(4) (P = 0.0001). In HY + T(4), plasma E(2) and PRL were similar to control. Vasoactive intestinal polypeptide increased in plasma of HY birds, but there was no effect of HS or HY + T(4). Immunoreactive VIP cells increased (P = 0.0036) in nucleus inferior hypothalami of HS and HY brains. In HY + T(4), VIP immunoreactive cell numbers were similar to control. It appears that HY induced chemically or by HS exerts similar effects on reproductive hormones in the hen; the results suggest involvement of the VIP-PRL pathway even though peripheral blood concentrations were not consistent between studies.

Topics: Animals; Chickens; Estrogens; Female; Hot Temperature; Hypothalamus; Hypothyroidism; Iodide Peroxidase; Oviposition; Progesterone; Prolactin; Reproduction; RNA, Messenger; Stress, Physiological; Thyroid Hormones; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) is a widespread neuropeptide involved in the autonomic nervous control of smooth muscle activity, blood flow and secretion. To study the biosynthetic processing of the VIP precursor in the gut of normal, hypo- and hyperthyroid rats we used antisera against the five functional domains of the precursor molecule, prepro-VIP 22-79, peptide histidine isoleucine (PHI), prepro-VIP 111-122, VIP and prepro-VIP 156-170, to quantify and characterize VIP precursor peptides by radioimmunoassay and chromatography and examine their cellular localization and co-localization by immunohistochemistry. All five peptides were expressed in the gut but not in equimolar amounts as expected from the structure of the VIP precursor. A high concentration of PHV, the C-terminally extended form of PHI which includes prepro-VIP 111-122, was found in the small intestine. Immunohistochemically the prepro-VIP derived peptides were shown to coexist in neuronal elements. Changes in thyroid hormone status induced moderate changes in peptide expression in the gut, the most prominent being a 2-fold increase in all prepro-VIP derived peptides in the gastric fundus of hypothyroid rats. The findings indicate that differences in the post-translational processing of prepro-VIP exist in neurons of the rat gut and that hypo- and hyperthyroidism induce differential changes in peptide expression.

Topics: Animals; Chromatography, Gel; Chromatography, High Pressure Liquid; Colon; Digestive System; Gastric Fundus; Hyperthyroidism; Hypothyroidism; Immune Sera; Immunohistochemistry; Intestine, Small; Male; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

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

Recent studies have shown that primary hypothyroidism induced in the rat was able to stimulate the biosynthesis of vasoactive intestinal peptide (VIP) in the anterior pituitary (AP). Since the AP VIP is known to stimulate prolactin (PRL) secretion through a paracrine and/or autocrine mechanism, it is interesting to hypothesize that hyperprolactinemia seen in hypothyroid patients may at least in part be due to a paracrine effect of elevated VIP on AP PRL secretion. Prompted by this information, we in the present study examined the effect of VIP load on PRL secretion in patients with primary hyperthyroidism or hypothyroidism, and compared the data with those from thyrotropin-releasing hormone (TRH) load performed in the same patients. Eight female patients with Graves' disease and 8 females with chronic thyroiditis received intravenous bolus injections of VIP (100 micrograms) and TRH (500 micrograms) 2-3 days apart from each other, during both the dysthyroid and euthyroid (attained by medical treatment) states. Compared to the data in the euthyroid state of the respective group, hyperthyroidism was associated with a lower basal PRL level and a lower PRL responsiveness (estimated by net percent increase in PRL) to TRH, whereas hypothyroidism was associated with higher values of these parameters. With respect to VIP, although the peptide was able to significantly stimulate PRL secretion during both the dysthyroid and euthyroid states of hyper- and hypothyroid patients, PRL responsiveness to VIP was essentially the same regardless of thyroid status.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Case-Control Studies; Female; Growth Hormone; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Prolactin; Thyrotropin; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

We report here data on the expression of the various sequences derived from the prepro-vasoactive intestinal polypeptide (VIP) precursor and VIP mRNA in the anterior pituitary gland and cerebral cortex of hypothyroid and hyperthyroid rats. Using specific antisera to each of the prepro-VIP sequences we demonstrated an increase of all prepro-VIP derived sequences, and accordingly, found that the number of cells expressing each of these sequences were markedly augmented in the anterior pituitary of the hypothyroid rats. This was accompanied by a marked increase in VIP mRNA. In the cerebral cortex of the hypothyroid rats no changes were observed. In the pituitary of hyperthyroid animals a significant decrease was seen for prepro-VIP 22-79, VIP and prepro-VIP 156-170, whereas in the cerebral cortex a significant increase was observed for prepro-VIP 22-79, PHI and VIP. We were not able to demonstrate any changes in VIP mRNA in the cerebral cortex or pituitary of the hyperthyroid rats. Gel permeation chromatography and reverse-phase HPLC of extracts from cerebral cortex showed elution profiles identical to the synthetic counterparts. The reported data provide further evidence of a tissue-specific expression and regulation of the VIP gene products.

Topics: Animals; Blotting, Northern; Cerebral Cortex; Chromatography, Gel; Chromatography, High Pressure Liquid; Gene Expression; Hyperthyroidism; Hypothyroidism; Immunohistochemistry; In Situ Hybridization; Male; Pituitary Gland, Anterior; Protein Precursors; Radioimmunoassay; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Hormones; Vasoactive Intestinal Peptide

A role of thyroid hormone in the regulation of neuropeptide synthesis has been demonstrated in different tissues. In this paper we investigated the vasoactive intestinal peptide (VIP) mRNA expression by means of in situ hybridization in several brain areas of hypo- and hyperthyroid adult rats. Neither hypo- nor hyperthyroidism modified the VIP mRNA levels in the thalamus and in the hypothalamic suprachiasmatic nucleus. In contrast, in the anterior cingulate and frontoparietal motor cortex of hypothyroid rats there was a marked increase in the signal for VIP mRNA per cell, but the number of VIP expressing neurons did not change. These data indicate that also central VIP synthesis can be influenced by the levels of circulating thyroid hormone, but that this effect is confined to specific areas and cell populations of the brain.

Topics: Animals; Brain Chemistry; Cell Count; Gene Expression Regulation; Gyrus Cinguli; Hyperthyroidism; Hypothyroidism; Male; Motor Cortex; Nerve Tissue Proteins; Neurons; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Hormones; Vasoactive Intestinal Peptide

We examined whether hypothyroidism-induced increases in the anterior pituitary content of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) are mediated by the hypothalamus. Male Sprague-Dawley rats were anesthetized and one of the following surgeries was performed: (1) sham thyroidectomy, (2) thyroidectomy, (3) thyroidectomy plus surgical anterolateral deafferentation of the medial basal hypothalamus, or (4) thyroidectomy and sham deafferentation of the hypothalamus (knife was inserted but not rotated). Two weeks after surgery, animals were killed and tissue samples collected for measurement of the anterior pituitary VIP and NPY and plasma thyroid-stimulating hormone (TSH), thyroxine, and prolactin concentrations (by RIA). Reverse-phase HPLC showed that VIP and NPY immunoreactivities in the anterior pituitary extracts are eluted in the positions identical to synthetic VIP and NPY, respectively. Only data from those animals with complete symmetric cuts located at the posterior border of the optic chiasm were included for analysis. In the thyroidectomized rats the anterior pituitary contents of VIP and NPY were significantly increased. These responses were almost completely prevented by the anterolateral deafferentation of the hypothalamus. Sham hypothalamic deafferentation had no effect on the pituitary neuropeptide responses to hypothyroidism. Anterolateral deafferentation of the hypothalamus also significantly blunted plasma TSH responses to hypothyroidism. These data suggest that some hypothalamic factor is involved in the mediation of the effect of hypothyroidism on the pituitary content of VIP and NPY.

Topics: Afferent Pathways; Animals; Chromatography, High Pressure Liquid; Denervation; Hypothalamic Area, Lateral; Hypothyroidism; Male; Neuropeptide Y; Organ Size; Pituitary Gland, Anterior; Rats; Rats, Sprague-Dawley; Thyroid Gland; Thyrotropin; Vasoactive Intestinal Peptide

VIP is an established prolactin-releasing factor. VIP gene expression at the anterior pituitary level and the central nervous system is regulated by thyroid hormones. On the other hand, primary hypothyroidism leads in many cases to amenorrhea, galactorrhea and hyperprolactinemia. In this study we assessed prolactin responses to VIP (75 micrograms iv infusion over 12 min) in a group of six hypothyroid women (mean age +/- SE, 38.8 +/- 3.3 yr; serum TSH levels, mU/L, 116.3 +/- 23.9), before treatment and after normalization of thyroid hormone levels during thyroxine (T4) replacement therapy (100-150 micrograms/day over 12-16 weeks). Furthermore, we assessed if VIP infusion had any effects on serum GH levels in these patients. In hypothyroid women, VIP infusion increased serum prolactin concentrations with peak levels being attained at 15 min (28.8 +/- 3.4 micrograms/L). The Area Under the Curve (AUC) was 1921 +/- 103 micrograms/L/2h. PRL responses to VIP were unchanged after T4 therapy, both in terms of peak levels (28.7 +/- 2.2 micrograms/L, NS) and of AUC (2079 +/- 261 micrograms/L/2h, NS). Serum GH levels were unaffected by VIP administration. In conclusion our study shows that, in hypothyroid patients, restoration of normal thyroid hormone levels by thyroxine replacement therapy does not affect lactotroph responsiveness to VIP. Therefore, our data do not support the hypothesis that VIP might contribute to the hypothyroid-induced hyperprolactinemia seen in man.

Topics: Adult; Blood Pressure; Female; Follicular Phase; Growth Hormone; Heart Rate; Humans; Hypothyroidism; Middle Aged; Prolactin; Thyroid Hormones; Thyroxine; Vasoactive Intestinal Peptide

The aim of the present study was to evaluate the time-dependent effect of an experimentally induced hypothyroid state on prolactin (PRL) secretion in rats. Treatment with radioactive iodine and propylthiouracil (PTU) resulted in reduced serum concentrations of total thyroxine and triiodothyronine, and increased serum TSH concentrations in rats one week after the start of the treatment. Basal serum PRL concentrations were not significantly altered in 1-, 2- and 4-week hypothyroid rats, whereas in 8-week hypothyroid rats, serum PRL concentrations were significantly reduced and remained depressed throughout 24 weeks of PTU ingestion. The PRL response to i.p. administration of haloperidol (0.5mg/kg) was significantly reduced after one week of PTU ingestion. When the duration of hypothyroidism was increased, there was a progressive fall in the PRL response to haloperidol that reached the lowest value after 12 weeks of PTU ingestion. The PRL response to an i.v. bolus injection of vasoactive intestinal peptide (VIP, 150 mu g/kg) was markedly reduced in hypothyroid rats after one week of PTU ingestion and reached the lowest value after two weeks. The PRL response to VIP was progressively recovered after treatment for 4 weeks with PTU, and reached the highest value in 24-week hypothyroid rats. However, the PRL response to VIP in 24-week hypothyroid rats was significantly lower than that in euthyroid rats. Serum PRL response to an i.v. bolus injection of beta -endorphin (450 mu g/kg) was significantly reduced in 8-week hypothyroid rats. Dopamine (DA) concentrations in the pituitary and the hypothalamus were not significantly altered in 2-week hypothyroid rats. In contrast, DA concentrations were significantly increased in both the pituitary and hypothalamus in 8- and 24-week hypothyroid rats. These findings observed in hypothyroid rats were reversed by the administration of thyroxine and triiodothyronine for 9 days. The present results support a modulatory role for thyroid status in regulating the concentration of DA in the pituitary and the hypothalamus, and consequently on PRL secretion by the pituitary. This suggests that PRL releasing factors do not appear to play a major role in PRL secretion in hypothyroid rats. These data also indicate that alterations in PRL secretion and DA concentrations in the pituitary and the hypothalamus in the hypothyroid state become more prominent as the duration of hypothyroidism increases.

Topics: Animals; beta-Endorphin; Dopamine; Haloperidol; Hypothalamus; Hypothyroidism; Male; Pituitary Gland; Prolactin; Rats; Rats, Wistar; Time Factors; Vasoactive Intestinal Peptide

The effect of vasoactive intestinal peptide (VIP) on thyroxine type II 5'-deiodinase (5'-D) and N-acetyltransferase (NAT) activities were studied using pineal cells of euthyroid and hypothyroid rats. VIP activated 5'-D activity in a dose-dependent manner in both euthyroid and hypothyroid animals. However, basal and VIP stimulated activity was higher in pinealocytes from hypothyroid than in cells from euthyroid rats. VIP was also able to stimulate NAT activity but hypothyroidism did not induce modifications in its activity. Both 5'-D and NAT activities were stimulated not only by VIP, but also by isoproterenol, a beta-adrenergic receptor agonist, and forskolin, a potent activator of adenylate cyclase activity. The results suggest that VIP may be involved in the physiological regulation of pineal 5'-D activity.

Topics: Animals; Arylamine N-Acetyltransferase; Colforsin; Hypothyroidism; In Vitro Techniques; Iodide Peroxidase; Iodine Radioisotopes; Isoproterenol; Pineal Gland; Propranolol; Rats; Vasoactive Intestinal Peptide

Using in situ hybridization histochemistry, we have investigated the effect of thyroid hormone on the expression of several peptide mRNAs in the hypothalamic paraventricular nucleus (PVN) of adult male rats. Hypothyroidism was induced by surgical ablation of the thyroid gland. The animals (control sham-operated, thyroidectomized, thyroidectomized+T4 replaced rats) were studied 28 and 50 days after surgery. Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), galanin (GAL), enkephalin (ENK), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and vasopressin (VP). GAL mRNA was also analyzed in the anterior paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus. At the PVN level, a feedback effect of thyroid hormone on TRH synthesis was demonstrated by the TRH mRNA increase in hypothyroidism and by its decrease in hyperthyroidism. Hypothyroidism caused a dramatic decrease in GAL mRNA in parvo- and magnocellular PVN neurons both 28 and 50 days after thyroid ablation, whereas no effect was seen in VP mRNA, the main peptide hormone coexisting with GAL. The T4 replacement prevented the GAL mRNA impairment. Hypothyroidism did not influence GAL mRNA in the anterior PVN, perifornical area or in the arcuate nucleus, whereas a decrease in GAL mRNA was observed in the dorsomedial nucleus. VIP mRNA, which is undetectable in the PVN of normal animals, was present in several PVN neurons after thyroidectomy. CRH mRNA was decreased after thyroidectomy, whereas the T4 restitution caused an upregulation. The levels of ENK or NT mRNA were not significantly affected by the thyroid status. The present results show that, in addition to TRH mRNA, other hypothalamic peptide mRNAs are affected by thyroid hormone levels.

Topics: Animals; Corticotropin-Releasing Hormone; Enkephalins; Galanin; Hypothalamic Hormones; Hypothalamus; Hypothyroidism; In Situ Hybridization; Male; Neurotensin; Paraventricular Hypothalamic Nucleus; Peptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine; Vasoactive Intestinal Peptide; Vasopressins

Vasoactive intestinal polypeptide (VIP) is produced by neurons in the rat hypothalamic paraventricular nucleus (PVN) and may have an important role as a prolactin-releasing factor. Recent work from our laboratories has shown that thyroid hormone regulates the content of VIP and VIP mRNA in the rat anterior pituitary, but its effect on VIP in the PVN is not known. To determine whether thyroid hormone alters VIP biosynthesis in the PVN, we studied the effect of hypothyroidism on the content of immunoreactive (IR)-VIP and VIP mRNA in PVN neurons using histochemical techniques. By immunocytochemistry, only scattered IR-VIP fibers were present in the PVN of control animals whereas IR-VIP perikarya and fibers were present in hypothyroid rats. By in situ hybridization histochemistry, no labeled neurons were recognized in the PVN in control animals whereas PVN neurons were labeled in hypothyroid rats. These findings raise the possibility that hypothyroidism exerts negative feedback regulation on VIP-producing neurons in the PVN and suggest that this may be important to modulate the stimulatory effects of VIP on anterior and/or posterior pituitary function.

Topics: Animals; Gene Expression; Hypothyroidism; Immunoenzyme Techniques; Male; Nucleic Acid Hybridization; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; RNA, Messenger; Vasoactive Intestinal Peptide

To determine the effects of hypothyroidism and sexual dimorphism on the gene expression of vasoactive intestinal peptide (VIP) in the rat brain, VIP mRNA levels were measured in the cerebral cortex, hypothalamus and anterior pituitary of control and hypothyroid (thionamide-treated) rats. A tissue-specific increase in VIP mRNA level was observed in the hypothyroid pituitary. In addition, higher levels of VIP mRNA were found in the pituitaries of male rats suggesting a sex-related difference in VIP gene expression. Similar differences were not observed in the cortex or hypothalamus.

Topics: Animals; Brain; Female; Gene Expression Regulation; Hypothyroidism; Male; Organ Specificity; Pituitary Gland, Anterior; Rats; Rats, Inbred Strains; RNA, Messenger; Sex Characteristics; Thyroid Hormones; Vasoactive Intestinal Peptide

In this study, we demonstrated that the cell content and basal secretion of vasoactive intestinal peptide (VIP) in primary rat pituitary cell cultures were increased in hypothyroidism. VIP release from hypothyroid pituitary cells in vitro was stimulated by thyrotropin releasing hormone (TRH 10(-8) to 10(-6) M) and growth hormone (GH)-releasing hormone (GHRH 10(-9) to 10(-8) M) but not by corticotropin-releasing hormone or luteinizing hormone-releasing hormone in concentrations up to 10(-6) M. In the presence of anti-VIP antisera, there was a significant decrease in basal prolactin secretion from cultured hypothyroid pituitary cells (p less than 0.005) indicating that VIP exerts a tonic stimulatory effect on prolactin (PRL) secretion. The increment in PRL secretion following TRH was not affected by exposure to anti-VIP indicating that PRL release after TRH is not mediated by VIP at the pituitary level. In contrast to changes in PRL, exposure to anti-VIP had no effect on basal GH secretion, indicating that the PRL changes are hormone specific. Similarly, GHRH-induced GH release was unaffected by VIP immunoneutralization.

Topics: Animals; Growth Hormone; Growth Hormone-Releasing Hormone; Hypothyroidism; In Vitro Techniques; Male; Pituitary Gland; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Vasoactive Intestinal Peptide

The binding of vasoactive intestinal peptide (VIP) and stimulation of adenylate cyclase by VIP were studied in intestinal epithelial cells during hypothyroidism. Experimental hypothyroidism was induced in rats by the administration of KC10(4). The binding capacity, but not the affinity, of VIP receptors decreased in the hypothyroid rats. Besides, the stimulation of cyclic AMP production by VIP was also diminished in cells from hypothyroid rats. These observations indicate a decrease of the responsiveness of intestinal epithelial cells to VIP in the hypothyroid status, suggesting a role of the peptide in the pathophysiologic mechanism of intestinal manifestations during hypothyroidism.

Topics: Animals; Cyclic AMP; Epithelium; Hypothyroidism; Intestinal Mucosa; Intestines; Kinetics; Male; Perchlorates; Potassium; Potassium Compounds; Rats; Rats, Inbred Strains; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

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

Vasoactive intestinal peptide (VIP) and PRL have been reported to be colocalized in rat lactotropes. To determine whether induced hypothyroidism, known to reduce pituitary PRL concentration, also reduces pituitary concentration of VIP, rats were treated with antithyroid drugs for 3 weeks. Pituitary PRL concentration in male rats (micrograms/mg protein) was markedly reduced by this treatment (9.4 +/- 1.0 vs. 2.3 +/- 0.4 when extracted at pH 1.1, 17.9 +/- 3.0 vs. 3.4 + 0.4 when extracted at pH 7.4, 21.8 +/- 3.3 vs. 6.7 + 1.3 when extracted at pH 10.0). Contrary to expectation, pituitary VIP concentration was markedly increased in hypothyroidism; in males from 169.5 +/- 20.3 to 834.0 +/- 82.2 pg/mg protein, and in females (whose pituitary PRL had been similarly reduced) from 103.1/I +/- 34.1 to 771.6 +/- 100.9 pg/mg protein. Serum PRL was significantly reduced in hypothyroid males (7.4 +/- 1.6 vs. 28.9 +/- 12.2 ng/ml) whereas in females, serum PRL was not significantly altered (41.4 +/- 11.6 vs. 38.8 +/- 14.3 ng/ml). The effect of hypothyroidism was reversed by administration of T4 in physiological doses. The authenticity of pituitary immunoreactive VIP was further established by demonstrating chromatographic patterns by Sephadex G-50 gel exclusion and reverse phase HPLC separations identical to synthetic VIP. Immunohistochemically reactive VIP cells could not be demonstrated in normal pituitaries, but the marked increase in VIP in hypothyroid animals made it possible to visualize a population of VIP immunoreactive stellate cells which appear to be distinct from hypothyroid lactotropes and thyrotropes.

Topics: Animals; Female; Hypothalamus; Hypothyroidism; Male; Pituitary Gland, Anterior; Prolactin; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Triiodothyronine; Vasoactive Intestinal Peptide

The effect of changes in thyroid function upon vasoactive intestinal peptide (VIP) induced secretion of saliva were studied in male Wistar rats. Hyperthyroidism was induced by the sc administration every 12 h of 10 micrograms/100 g bw of I-triiodothyronine; hypothyroidism was induced by surgical thyroidectomy 2 weeks before the experiments. Preganglionar parasympathetic denervation was induced by sectioning the chorda tympani on the left side. The dose-response curves to increasing doses of VIP showed in the hypothyroid animals increased salivary secretion, while in the hyperthyroid ones the dose-response to the drug was reduced. This effect was seen on both sides, the denervated and the control ones. In the denervated glands there was a marked hypersensitivity to the administration of VIP producing greater responses with the same doses, in the 3 groups of animals. The negative modulation by thyroid hormones of the salivary response to VIP administration is compared with the positive modulation they induce in the salivary response to beta-adrenergic and cholinergic drugs.

Topics: Animals; Denervation; Dose-Response Relationship, Drug; Hyperthyroidism; Hypothyroidism; Male; Organ Size; Rats; Rats, Inbred Strains; Saliva; Submandibular Gland; Thyroid Hormones; Vasoactive Intestinal Peptide