Thyreotropin-releasing Hormone Research Articles

Neuroperptides, their interactions and gastric mucosal protection in the rat.

In the last decades several neuropeptides, such as thyreotropin‐releasing hormone (TRH), amylin, neurotensin, ghrelin, melatonin, opioid peptides, substance P (SP), angiotensin II (Ang II) have been shown inhibit the gastric mucosal lesions induced by different ulcerogenic agents given centrally in the dose range of fmol to nmol. The site of action is likely to be the dorsal vagal complex. However, the different neuropeptides can interact with each other at different levels and can affect each other's biological actions. Among others nociceptin ‐ opioid; angiotensin ‐ cannabinoid, opioid; CRF ‐ beta‐endorphin, somatostatin interactions have been demonstrated. Aim of the present study was to elucidate potential interactions between neuropeptides and cannabinoids in gastric mucosal defense.MethodsGastric damage was induced by acidified ethanol in the rat (150–170 g, males); the gastric mucosal lesions were detected 60 min after ethanol administration. The dugs were given intracerebroventricularly (i.c.v.) 10 min before ethanol challenge. Gastric mucosal CGRP, somatostatin levels were determined by RIA.ResultsThe gastroprotective effect of SP, nociceptin or cannabinoids was reversed by endomorphin2‐antiserum or the opioid receptor antagonist naloxone, while the Ang II‐induced protection was decreased by the CB1 receptor antagonists, AM‐251.ConclusionNeuropeptides have prominent role in central regulation of gastric mucosal integrity. In addition, interactions between neuropeptides result in redundancy in centrally‐initiated gastric mucosal defense.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Experimental Study of the Effects of the Hypothalamic-Pituitary-Thyroid Axis on Platelet Functional Activity

The hormones of the hypothalamic-pituitary-thyroid axis exert various effects in organism, but their influence on the functional activity of platelets is relatively unknown. To establish the effect of the hormones of the hypothalamic-pituitary-thyroid axis on the functional activity of platelets by means of determining the plasma level of beta-thromboglobulin (β-TG) and platelet factor 4 (PF4) a study was conducted on 40 white male rats of the “Wistar” breed. The necessary blood volume was obtained under ether narcosis by cardiac puncture in CTAD-test-tubes. Using Diagnostica Stago (France) tests, by means of enzyme-immune test, the level of two of the most informative platelet secretion markers was determined. The hormones: Thyreotropin releasing hormone (0.06 mg/kg bw), Thyroid stimulating hormone (1 MU/kg bw), Trijodthyroninum (0.08 mg/kg bw), Thyroxin (0.08 mg/kg bw), applied s.c. on three consecutive days strongly reduce the plasma level of β-TG (p<0.001) and PF 4 (p < 0.001). The reduced level of β-TG and PF 4 in the plasma is an indicator of their reduced functional activity, which is one of the determinants for the development of hemocoagulation. The functional activity of platelets in rats, determined by the level of β-TG and PF 4, is significantly suppressed by all hormones of the hypothalamic-pituitary-thyroid axis.

PreproTRH(158–183) fails to affect pituitary-adrenal response to CRH/vasopressin in man: A pilot study

Non-glucocorticoid inhibitors of the HPA-system are of utmost interest in the treatment of diseases with impaired regulation of this system, like the metabolic syndrome and depression. In rats, a fragment of the thyreotropin-releasing hormone (TRH) preprohormone, preproTRH((178-199)), has been demonstrated to inhibit basal and stimulated secretion of cortisol. Our pilot study aimed to explore the first time similar effects of the homologue peptide preproTRH((158-183)) in healthy humans. In a double-blind within-subject comparison, eight healthy young men were infused intravenously with placebo and preproTRH((158-183)) at varying doses of 5, 10, 25 and 50 mg/kg of body weight. After 15 min of infusion a corticotropin-releasing hormone (CRH)/vasopressin-test was performed. Plasma concentrations of pituitary hormones and free thyroxine, blood pressure, heart rate and feelings of activation and mood were assessed repeatedly at close intervals. Individual hormone profiles and collapsed data across all doses did not reveal any effects of preproTRH((158-183)) on HPA-activity, although it increased TSH and fT4, stimulated the release of GH and increased systolic blood pressure in the course of the experiment (p<0.05, for all effects). Self-reports indicated enhanced feelings of activation and general well-being following preproTRH (p<0.05). Our data exclude a substantial inhibitory effect of preproTRH((158-183)) on HPA secretory activity and, thus, contrast with findings in rats. In humans, the peptide appears to even exert an albeit weak stimulatory effect on autonomic stress systems as indicated by increased cardiovascular activity in combination with enhanced subjective arousal.

Neuropeptides and gastric mucosal homeostasis.

The role of central nervous system (CNS) in regulation of gastric function has long been known. The dorsal vagal complex (DVC) has an important role in regulation of gastric mucosal integrity; it is involved both in mucosal protection and in ulcer formation. Neuropeptides have been identified in DVC, the origin of these peptides are both intrinsic and extrinsic. Neuropeptides are localized also in the periphery, in afferent neurons. The afferent neurons also have efferent-like function in the gastroinetestinal tract, and neuropeptides released from the peripheral nerve endings of primary afferent neurons can induce gastric mucosal protection. Centrally and /or peripherally injected neuropeptides, such as amylin, adrenomedullin, bombesin, cholecystokinin, neurotensin, opioid peptides, thyreotropin releasing hormone and vasoactive intestinal peptide, influence both the acid secretion and the gastric mucosal lesions induced by different ulcerogens. The centrally induced gastroprotective effect of neuropeptides may be partly due to a vagal dependent increase of gastric mucosal resistance to injury; activation of vagal cholinergic pathway is resulted in stimulation of the release of mucosal prostaglandin and nitric oxide. Furthermore, release of sensory neuropeptides (calcitonin gene-related peptide, tachykinins) from capsaicin sensitive afferent fibers are also involved in the centrally induced gastroprotective effect of neuropeptides.

P.5.040 Thyreotropin-releasing hormone and cocaine sensitization in rats

P.5.040 Thyreotropin-releasing hormone and cocaine sensitization in rats

Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients

The symptomatology of the fibromyalgia syndrome (FMS) often resembles an alteration in central nervous set points at least in three systems. The patiens suffer under chronic pain in the region of the locomotor system, presumably reflecting a disturbed central processing of pain. Anxiety and depression often characterizes the clinical picture. Almost all of the hormonal feedback mechanisms controlled by the hypothalamus are altered. Characteristic for FMS patients are the elevated basal values of ACTH, follicle-stimulating hormone (FSH), and cortisol as well as lowered basal values of insulin-like growth factor 1 (IGF-1, somatomedin C), free triiodothyronine (FT3), and oestrogen. In FMS patients, the systemic administration of the relevant releasing hormones of corticotropin-releasing hormone (CRH), growth hormone-releasing hormone (GHRH), thyreotropin-releasing hormone (TRH), and luteinizing hormone-releasing hormone (LHRH) leads to increased secretion of ACTH and prolactin, whereas the degree to which TSH can be stimulated is reduced. The stimulation of the hypophysis with LHRH in female FMS patients during their follicular phase results in a significantly reduced LH response. All in all, the typical alterations in set points of hormonal regulation that are typical for FMS patients can be explained as a primary stress activation of hypothalamic CRH neurons caused by the chronic pain. In addition to the stimulation of pituitary ACTH secretion, CRH activates somatostatin on the hypothalamic level, which in turn inhibits the release of GH and TSH on the hypophyseal level. The lowered oestrogen levels could be accounted for both via an inhibitory effect of the CRH on the hypothalamic release of LHRH or via a direct CRH-mediated inhibition of the FSH-stimulated oestrogen production in the ovary. Serotonin (5HT), precursors like tryptophan (5HTP), drugs which release 5HT or act directly on 5HT receptors stimulate HPA axis, indicating a stimulatory serotonergic influence on HPA axis function. Therefore activation of the HPA axis may reflect an elevated serotonergic tonus in the central nervous system of FMS patients.

Synthesis, structure and biological activity of α-trifluoromethyl-substituted thyreotropin releasing hormone

The incorporation of α-trifluoromethyl pyroglutamic acid into thyreotropin releasing hormone TRH, results in the complete stability of the pGlu-His bond against proteolytic degradation by pyroglutamyl aminopeptidase II. The influence of the trifluoromethyl group on structure and receptor affinity has been studied.

Neuropeptides in the human superior cervical ganglion

Superior cervical ganglia from 7 human cadavers (3–7 h post mortem) were immunostained for tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and 14 different neuropeptides. The results show that ganglionic cells contain TH, DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). These substances were present predominantly within large ganglionic cells. Inside the ganglion, the number and topographical distribution of various types of immunoreactive cells differed from one another. NPY and CGRP immunoreactivities were found in some TH-positive cells, but that co-localization never exceeded the 30% of the TH cells. Leu-enkephalin showed a weak immunoreactivity, which was restricted to fibers or varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin, galanin, corticotropin-releasing factor, thyreotropin-releasing hormone, angiotensin II and neurotensin showed no immunoreactivity in the human superior cervical ganglion.

Fast, short-term response to TRH stimulation in geriatric patients and its clinical importance

In 52 geriatric patients, average age of 74 years (range from 65 to 89) suffering from generalised arteriosclerotic disease and hospitalized at the Clinical Institute for Geriatrics, we found normal thyroid gland function, in basal condition. Our data showed that 19.42% of the patients had low triiodothyronine (T 3) concentrations. Basal serum T 3 level was higher ( P < 0.01) in males (1.88 ± 0.44 nmol/l) in comparison to values in females (1.75 + 0.28). Serum thyroxine (T 4) level was lower in males ( P < 0.01), but the concentrations of thyreo stimulating hormone (TSH) was lower in females. The value of thyroid reserve in elderly people, estimated by measuring T 3 and T 4 incretion shortly after thyreotropin releasing hormone (TRH) was done, is sufficient to maintain cuthyroid function, although it is, as a whole, significantly lower if compared with T 4 and T 3 response after TRH tests in middle-aged subjects ( n = 26), acting as a control group ( P < 0.001). Thyroxine excretion from follicular cells in elderly female patients was faster and amplitude was higher, up to the maximal possible level 93 nmol/l (± SD) in 25 min after an injection of TRH. In elderly male patients the maximum of T 4 excretion was 78 nmol/l ( P < 0.01) at 60 min.

Hormone load tests in infertile male patients.

The recognition that discreet hormonal abnormalities may cause ovulation disorders in women suggested that the male partner of infertile women might also suffer from unrecognized hormonal dysfunction amendable to substitution therapy. We obtained a combined stimulation test with gonadotropin-releasing hormone (GnRH), thyreotropin-releasing hormone (TRH), and ACTH in 225 males with childless spouses, when the couple sought to have children for at least one year. The following hormone levels were determined: estradiol (E), thyroid-stimulating hormone (TSH), prolactin, testosterone (T), dihydrotestosterone (DHT), androstenedione(A), 17-OH-pregnenolone (17-OH-Preg), 17-OH-progesterone (17-OHP), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisone (F), and 21-desoxycortisone (21DF). Basal and stimulated, and adrenal-testicular steroids with and without ACTH stimulation failed to demonstrate a relevant relationship to semen parameters. Gonadotropin levels had a significant negative correlation to all important semen parameters (testicular volume, sperm count, motility, morphology, and vitality) and were positively correlated to spermiogenetic defects. Stimulated LH values were more clearly associated with spermiogenetic defects than basal LH. Nonetheless, basal FSH concentrations were more informative than LH. Stimulated prolactin values were positively correlated with both gonadotropin and with sperm morphology. E concentrations had a significant positive correlation with both basal and poststimulation DHEAS values, and showed a highly negative correlation with sperm count, morphology, and vitality. In comparison, good sperm parameters were associated with high poststimulation T concentrations. The results of this study suggest that basal FSH and E concentrations, as well as the stimulated LH, T, and prolactin determinations, should be included in the evaluation of male sterility.

Immunoreactivity to vasoactive intestinal polypeptide (VIP) and thyreotropin-releasing hormone (TRH) in hypothalamic neurons of the domesticated pigeon (Columba livia). Alterations following lactation and exposure to cold.

The distribution of VIP- and TRH-immunoreactivity in neurons and processes within the hypothalamus of the pigeon was investigated with light-microscopic immunocytochemical techniques. Most of the VIP-containing neurons are concentrated in the middle and caudal parts of the hypothalamus, with the greatest concentration of perikarya occurring in the medial and lateral part of the ventromedial hypothalamic nucleus and the infundibular nucleus. These cells give rise to axons that seem to extend into the median eminence. An extensive network of VIP-immunoreactive fibers and varicosities occupy the external layer of the median eminence. The majority of TRH-containing neurons is found in the anterior hypothalamus with the greatest concentration of cells in the magnocellular preoptic, medial preoptic, suprachiasmatic and paraventricular nuclei. TRH-immunoreactive fibers and varicosities form a dense arborization in the external layer of the median eminence. Lactation seems to induce substantial changes in VIP as well as in TRH-immunostaining in the median eminence and other hypothalamic regions as compared to control, sexually active animals. Furthermore, TRH-immunoreactivity decreased in the median eminence following 60-min exposure to cold. These results suggest that VIP- and TRH-containing pathways in the pigeon hypothalamus are involved in the mediation of neuroendocrine responses.

Serum prolactin and thyroid stimulating hormone levels following thyreotropin releasing hormone stimulation in preeclamptic patients.

Serum prolactin and thyroid stimulating hormone (TSH) levels were measured following administration of thyreotropin releasing hormone (THR) in 17 preeclamptic patients and 18 normal pregnant controls. From the 31st to the 35th pregnancy week the preeclamptic patients showed increased basal serum prolactin and TSH levels compared to controls, but later in pregnancy the differences disappeared. Following TRH stimulation, the serum prolactin and TSH responses were similar in women with and without preeclampsia. A possible role of prolactin in the development of preeclampsia is discussed.

Effects of cimetidine on the secretion of some pituitary hormones.

Cimetidine infused intravenously into 6 healthy volunteers did not induce significant changes in plasma levels of prolactin (hPRL), thyreotropin (hTSH), gonadotropin (hLH and hFSH) and growth hormone (hGH). Conversely it caused a significant increase in prolactin response to TRH without modifying the hTSH response to thyreotropin-releasing hormone (TRH) and gonadotropin response to gonadotropin-releasing hormone (GnRH). Data obtained in these experiments, together with data reported in the literature, suggest that the amplified prolactin response to TRH observed during cimetidine infusion, is likely to be connected with a blockade of H2-receptors rather than to unspecific actions of cimetidine.

Profil de la T.R.H. en psychopharmacologie exp�rimentale

The following behavioral modifications were observed after a single i.p. administration of T.R.H. (thyreo-tropin-releasing hormone) in mice or rats at doses higher than 4mg · kg−1:

Plasma cortisol levels following intravenous injection of thyreotropin releasing hormone (TRH) in man

Plasma cortisol levels following intravenous injection of thyreotropin releasing hormone (TRH) in man

Thyreotropin-releasing hormone and serum levels of H-TSH, HGH, thyroxine, insulin and glucose.

Thyreotropin-releasing hormone and serum levels of H-TSH, HGH, thyroxine, insulin and glucose.