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ABSTRACT
TRH increases the pressor response to acetylcholine through an increment in muscarinic receptors. As chronic atropinization produces a similar effect, we hypothesized that both phenomena may be related. The effect of chronic atropine treatment on the TRH content of several brain areas in Wistar rats was studied. Atropine produced significant increases in TRH content in the preoptic and septal areas, while decreases were observed in the hypothalamus and hypophysis. The concentration of TRH in cerebrospinal fluid rose significantly in atropine-treated rats compared with controls. A similar effect was observed with eserine, an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area slices from normal rats with Krebs–Ringer solution in the presence of pilocarpine increased basal TRH release significantly and this effect was blocked by atropine. These results are compatible with a muscarinic control on the activity of the central TRH system.
Journal of Endocrinology (1992) 134, 215–219
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SUMMARY
To determine how the sensitivity of the ectopic anterior pituitary gland to the GH-releasing effect of thyrotrophin releasing hormone (TRH) might be affected by the time lapse from transplantation, TRH (0·15 and 0·6 μg) was injected i.v. into hypophysectomized (hypox)-transplanted rats under urethane anaesthesia 1,3, 8,15, 30 and 60 days after transplantation, and plasma samples were taken 5 and 10 min later. Baseline GH values gradually decreased with time from about 16·0 ng/ml (1 day) to about 3·0 ng/ml (30 and 60 days). The TRH-induced GH release was absent 1 day after transplantation, present only with the higher TRH dose 3 and 8 days after transplantation, and clearly elicitable, also with the lower TRH dose (0·15 μg), from 15 up to 60 days. Determination of plasma prolactin concentrations showed a decline from about 85·0 ng/ml (1 day) to about 32·0 ng/ml (8 days); subsequently (15–60 days) prolactin values stabilized. Plasma prolactin levels increased 15 and 60 days after transplantation only when a dose of 0·6 μg TRH was given.
In intact weight-matched rats, TRH induced a GH response only at the dose of 1·2 μg while a short-lived but clear-cut prolactin response could be obtained even with the 0·3 μg dose.
The present results indicate that: (1) disconnexion between the central nervous system and the anterior pituitary gland greatly enhances GH responsiveness while blunting prolactin responsiveness to TRH; (2) the sensitivity of the anterior pituitary gland to the GH-releasing effect of TRH increases with time from transplantation; (3) TRH is a more effective prolactin-than GH-releaser on the pituitary gland in situ.
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The changes in adenohypophysial and hypothalamic content and in hypothalamic release of dopamine and thyrotrophin-releasing hormone (TRH) into the hypophysial portal system during the suckling-induced release of prolactin were investigated. An increase in peripheral plasma levels of prolactin was induced by mammary nerve stimulation in urethane-anaesthetized and by suckling in unanaesthetized lactating rats. In the unanaesthetized rat, suckling caused a decrease of dopamine levels in hypothalamus and adenohypophysis and a short-lasting small increase in hypothalamic TRH. Mammary nerve stimulation induced a transient decrease in dopamine levels and an increase in TRH levels in hypophysial stalk blood. To assess the significance of the observed changes in dopamine and TRH levels for prolactin release, these changes in dopamine and TRH were mimicked in lactating rats anaesthetized with urethane and pretreated with α-methyl-p-tyrosine (AMpT, a competitive inhibitor of catecholamine synthesis). Reducing hypothalamic dopamine secretion by treatment with AMpT increased peripheral plasma levels of prolactin from 15 to 477 ng/ml; an infusion with dopamine, resulting in plasma levels similar to those measured in hypophysial stalk plasma, reduced plasma levels of prolactin to 127 ng/ml. Neither a 50% reduction in dopamine infusion rate for 15 min nor administration of 100 ng TRH caused an appreciable change in plasma prolactin levels. However, when dopamine infusion was reduced by 50% for 15 min just before TRH was injected, then an increase in plasma levels of prolactin from 172 to 492 ng/ml was observed. Thus, the effectiveness of TRH in releasing prolactin in the lactating rat was enhanced when a transient decrease of dopamine levels occurred before treatment with TRH. It is concluded that the changes observed in dopamine and TRH levels in hypophysial stalk blood are involved in the suckling-induced prolactin release in an important manner.
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Abstract
A TRH-like peptide, fertilization-promoting peptide (FPP), is present in high concentrations in mammalian prostate and semen and enhances the fertilization potential of spermatozoa. In this study, we have examined the properties of the enzyme that degrades TRH and FPP in rabbit seminal plasma. The enzyme responsible had a pH optimum of approximately 7·0, was inhibited by serine (di-isopropyl flurophosphate) and thiol (N-ethylmaleimide) protease inhibitors, bacitracin and concentrations of Zn2+ naturally present in seminal plasma: these functional reagents are all known to be potent inhibitors of prolyl endopeptidase. The major product after incubation of [3H]TRH in seminal plasma for 100 min was acid TRH (deamidated TRH) which is also the product after incubation of TRH with prolyl endopeptidase. Our results are consistent with the enzyme responsible for degradation of TRH and FPP in seminal plasma being similar to prolyl endopeptidase. The enzyme identified in this study is secreted and is therefore likely to be different from prolyl endopeptidase characterized from porcine brain, because the latter enzyme is known to be located in the cytosolic compartment of the cell.
Journal of Endocrinology (1995) 144, 61–66
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ABSTRACT
The effects of tri-iodothyronine (T3) and TRH on prolactin mRNA accumulation in monolayer pituitary cell cultures prepared from both euthyroid and hypothyroid rats were investigated. Basal prolactin mRNA concentrations and prolactin release into culture medium were increased in hypothyroid cultures, the increase being related to the duration of hypothyroidism in vivo. The inhibitory effects of T3 seen in euthyroid cells were preserved in cells derived from hypothyroid animals, and the degree of inhibition was greater in cells from the most severely hypothyroid rats. However, the stimulation of prolactin synthesis and secretion induced by TRH in euthyroid cultures was not found in the hypothyroid cells. Hypothalamic and anterior pituitary TRH content were measured in similarly hypothyroid and euthyroid rats. A large hypothalamic pool of TRH was found, which was unchanged in hypothyroidism, whereas anterior pituitary TRH content was increased in the hypothyroid rats. The consequent down-regulation of anterior pituitary TRH receptors may explain the poor response of prolactin to TRH seen in vitro.
J. Endocr. (1987) 115, 497–503
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ABSTRACT
A new TRH-like peptide pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2) has recently been purified and characterized from both the rabbit prostate complex and human semen. In this study, TRH-immunoreactive peptides were extracted from anterior pituitary, posterior pituitary and hypothalamus and subjected to gel exclusion chromatography. For each tissue, TRH was resolved from pGlu-Glu-ProNH2 by anion-exchange chromatography at pH 7.6 In the anterior pituitary, 63% of the TRH immunoreactivity was chromatographically identical to pGlu-Glu-ProNH2 whereas in the posterior pituitary the new peptide represented less than 5% of the total TRH immunoreactivity. Only trace levels of pGlu-Glu-ProNH2 were observed in hypothalamus, suggesting that the acidic TRH-related peptide found in the anterior pituitary may not be of hypothalamic origin. The new TRH-like peptide was purified from whole pituitaries by gel exclusion and ion-exchange chromatography, followed by high power liquid chromatography and was shown to have chromatographic properties identical to pGlu-Glu-ProNH2. Amino acid analysis of the purified peptide revealed glutamic acid and proline residues in the ratio Glx:2 Pro:1, which is the expected composition of pGlu-Glu-ProNH2 after acid hydrolysis.
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ABSTRACT
Plasma TSH rhythms were measured in Brattleboro (DI) and control Long–Evans (LE) rats with an intracardiac catheter allowing repeated sampling in conscious unstressed animals. The TSH response to thyrotrophin-releasing hormone (TRH; 500 ng/100 g body weight) was also determined. Finally, hypothalamic and pancreatic TRH concentrations and TRH-degrading activity (TRH-DA) were measured by specific radioimmunoassay. Long–Evans rats had a 24-h rhythm with a major modulatory 8-h component. In DI rats, only the 24-h rhythm was detected. The mean 24-h rhythm-adjusted mean TSH level was higher in DI than in LE rats (1·38±0·05 and 1·14 ± 0·06 μg/l respectively, P<0·01). The peak TSH response to TRH was significantly increased in DI rats while the pituitary concentration of TSH was also higher (0·93 ± 0·09 vs 0·39± 0·06 μg/mg wet weight in LE, P<0·001). Hypothalamic TRH and TRH-DA were similar in both strains. The response to propyl-thiouracil-induced hypothyroidism was identical in both strains. We conclude that DI rats have a normal pituitary sensitivity to tri-iodothyronine but a central dysfunction in the pituitary environment leading to some alterations of TSH secretion.
J. Endocr. (1985) 105, 277–283
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ABSTRACT
Amplification of desensitization of TSH response to thyrotrophin-releasing hormone (TRH) may be important mechanisms in the regulation of its secretion. We have investigated this possibility in vitro, using monolayer culture of rat anterior pituitary cells. Cells (1–1·5 × 105/250 μl per well) were cultured for 72 h, exposed to TRH or dibutyryl cyclic AMP (dbcAMP) for 6 or 8 h, washed, and then treated for 4 h with various doses of TRH, or with K+ (55 mmol/l) as a non-specific secretagogue. Pretreatment with TRH (20 nmol/l) for 8 h reduced subsequent TSH release: basal release fell to 64% of the control value (1·01±0·10 μg/l pretreated, 1·58 ± 0·16 control) and release in response to TRH (100 nmol/l) to 69% of the control (2·7 ± 0·19 μg/l vs 3·98 ± 0·22); K+ response was reduced to 86% of the control (3·77 ± 0·21 μg/l vs 4·39 ± 0·20), significantly less than the other reductions. The extent of the parallel downward shift of the TRH dose–response curve was proportional to dose and duration of prior TRH exposure. There was no significant change in the dose of TRH required to cause half-maximal TSH release (ED50: pretreated 4·8, control 2·8 nmol TRH/l) suggesting depletion of an intracellular pool of TSH rather than 'desensitization'. After 6-h pretreatment with dbcAMP, subsequent TSH responses were augmented: basal release was 130% of the control, response to TRH (100 nmol/l) was 137% and to K+ it was 132% of the control, with a parallel upward shift of the TRH dose–response curve but no change in cellular TSH content. We suggest that an intracellular pool of TSH exists which can be depleted by prior TRH exposure without a desensitization effect. The size of this pool may be increased by dbcAMP, indicating that cyclic nucleotides may modulate the availability of TSH to an acutely releasable intracellular pool.
J. Endocr. (1986) 108, 211–217
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Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but thereafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88–93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.
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ABSTRACT
Thyrotrophin-releasing hormone (TRH) stimulates GH secretion in domestic fowl by actions at pituitary and central nervous system sites. The possibility that this central action might be mediated by hypothalamic catecholamines or indoleamines was therefore investigated. When TRH was administered into the lateral ventricles of anaesthetized fowl the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC, a metabolite of dopamine (DA)) in the medial basal hypothalamus (MBH) was increased within 20 min. The concentrations of MBH noradrenaline (NA), DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were, however, unaffected by the intracerebroventricular (i.c.v.) administration of TRH, although the MBH concentrations of somatostatin and TRH were concomitantly reduced. A rapid increase in DA release into MBH extracellular fluid and its metabolism to DOPAC was also observed after i.c.v. or i.v. administration of TRH, in birds in which the MBH was perfused in vivo with Ringer's solution. Microdialysate concentrations of NA, 5-HT and 5-HIAA were not, however, affected by central or peripheral injections of TRH. Diminished GH responses to i.v. TRH challenge occurred in birds pretreated with reserpine (a catecholamine depletor), α-methyl-paratyrosine (a DA synthesis inhibitor) and pimozide (a DA receptor antagonist). These results therefore provide evidence for the involvement of a hypothalamic dopaminergic pathway in the induction of GH release following the central or peripheral administration of TRH. In contrast with its inhibitory actions at peripheral sites, DA would appear to have a central stimulatory role in regulating GH release in birds.
Journal of Endocrinology (1993) 138, 225–232
