Inhibitory Effect Of Thyrotropin-releasing Hormone Research Articles

Thyrotropin-releasing hormone and somatostatin inhibit each others release in vitro in the rat retina.

The effect of thyrotropin-releasing hormone (TRH), somatostatin (SS) or octreotide, an analogue of SS, on release of TRH or SS from the rat retina was studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin (medium) for 20 min. The amount of TRH or SS release into the medium was measured by individual radioimmunoassays. The TRH release from the rat retina was inhibited significantly in a dose-related manner by the addition of SS or octreotide. The SS release from the retina was inhibited by TRH, and the inhibitory effect of TRH on SS release from the rat retina was blocked by the addition of anti-TRH receptor antiserum immunoglobulin fraction. The findings suggest an interaction between TRH and SS in the rat retina by which the addition of one inhibits the release of the other.

Thyrotropin releasing hormone interactions with growth hormone secretion in horses.

Light horse mares, stallions, and geldings were used to 1) extend our observations on the thyrotropin releasing hormone (TRH) inhibition of GH secretion in response to physiologic stimuli and 2) test the hypothesis that stimulation of endogenous TRH would decrease the normal rate of GH secretion. In Exp. 1 and 2, pretreatment of mares with TRH (10 microg/kg BW) decreased (P < 0.001) the GH response to exercise and aspartate infusion. Time analysis in Exp. 3 indicated that the TRH inhibition lasted at least 60 min but was absent by 120 min. Administration of a single injection of TRH to stallions in Exp. 4 increased (P < 0.001) prolactin concentrations as expected but had no effect (P > 0.10) on GH concentrations. Similarly, 11 hourly injections of TRH administered to geldings in Exp. 5 did not alter (P > 0.10) GH concentrations either during the injections or for the next 14 h. In Exp. 5, it was noted that the prolactin and thyroid-stimulating hormone responses to TRH were great (P < 0.001) for the first injection, but subsequent injections had little to no stimulatory effect. Thus, Exp. 6 was designed to determine whether the inhibitory effect of TRH also waned after multiple injections. Geldings pretreated with five hourly injections of TRH had an exercise-induced GH response identical to that of control geldings, indicating that the inhibitory effect was absent after five TRH injections. Retrospective analysis of pooled, selected data from Exp. 4, 5, and 6 indicated that endogenous GH concentrations were in fact lower (P < 0.01) from 45 to 75 min after TRH injection but not thereafter. In Exp. 7, 6-n-propyl-2-thiouracil was fed to stallions to reduce thyroid activity and hence thyroid hormone feedback, potentially increasing endogenous TRH secretion. Treated stallions had decreased (P < 0.01) concentrations of thyroxine and elevated (P < 0.01) concentrations of thyroid-stimulating hormone by d 52 of feeding, but plasma concentrations of GH and prolactin were unaffected (P > 0.10). In contrast, the GH response to aspartate and the prolactin response to sulpiride were greater (P < 0.05) in treated stallions than in controls. In summary, TRH inhibited exercise- and aspartate-induced GH secretion. The duration of the inhibition was at least 1 h but less than 2 h, and it waned with multiple injections. There is likely a TRH inhibition of endogenous GH episodes as well. Reduced thyroid feedback on the hypothalamic-pituitary axis did not alter basal GH and prolactin secretion.

Involvement of nicotinergic mechanisms in thyrotropin-releasing hormone-induced neurologic recovery after concussive head injury in the mouse

A behavioral study was performed in an attempt to understand the neuronal mechanisms involved in the thyrotropin-releasing hormone (TRH)-induced improvement of consciousness after concussive head injury in the mouse. Intravenous administration of TRH dose dependently shortened the duration of unconsciousness after concussion in the mouse (ED 50=3.2 mg/kg). The improvement of recovery evoked by TRH (3 mg/kg i.v.) after concussion was not affected by i.p. pretreatment with N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine, α-methyl- para-tyrosine, p-chlorophenylalanine, scopolamine or methylscopolamine. However, mecamylamine or hexamethonium i.p. pretreatment completely inhibited the TRH-induced improvement of outcome in traumatic brain injury. The results imply that TRH-induced improvement of recovery after concussion is not associated with increased activity of monoaminergic neurons in the brain. These results suggest that the inhibitory effect of TRH upon unconsciousness after concussion in mice is mainly produced by activation of central cholinergic systems via nicotinic receptors whereas muscarinic receptors seem to be not implicated.

Thyrotropin-releasing hormone (TRH) inhibits vasopressin and oxytocin release from rat hypothalamo-neurohypophysial explants in vitro.

Incubation of hypothalamo-neurohypophysial explants in Locke's solution containing 28 nM/L thyrotropin-releasing hormone (TRH) resulted in an inhibition of vasopressin and oxytocin secretion during depolarization due to excess potassium. These data suggest the involvement of TRH in the regulatory mechanisms of vasopressin and oxytocin release; the inhibitory effect of TRH cannot be excluded.

Direct inhibitory effect of thyrotropin-releasing hormone on isolated cecal circular smooth muscle cells of guinea pig.

Smooth muscle cells isolated from cecal circular smooth muscle of the guinea pig were used to determine whether thyrotropin-releasing hormone (TRH) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine (an inhibitor of adenylate cyclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of nitric oxide synthase) on the TRH-induced relaxation of cecal circular smooth muscle cells was examined. TRH inhibited the contractile response produced by 10(-6) M carbachol in a concentration-dependent manner, with an IC50 value of 4 nM, 2',5'-Dideoxyadenosine and phorbol 12-myristate 13-acetate did not have any significant effect on the TRH-induced relaxation. On the other hand, 6-anilinoquinoline-5,8-quinone and N omega-nitro-L-arginine methyl ester significantly inhibited the relaxation produced by TRH. Our findings show that TRH has a direct inhibitory effect on the isolated cecal circular smooth muscle cells via activation of nitric oxide synthase and soluble guanylate cyclase.

Inhibitory Effect of Thyrotropin-Releasing Hormone on Enzyme Secretion from Isolated Rat Pancreatic Acinar Cells

This study reports a direct effect of TRH on amylase secretion from isolated rat exocrine pancreatic acinar cells. TRH inhibited carbachol (10(-5) M)-stimulated amylase secretion by a maximum of 24% at a concentration of 10(-11) M (p < 0.05), but did not affect basal amylase release in concentrations from 10(-13) M to 10(-8) M. Ceruletide (3 x 10(-10) M)-stimulated amylase secretion was maximally reduced by 23% at a TRH concentration of 10(-10) M (p < 0.05). Direct stimulation of protein kinase C-mediated secretion by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) was not altered by TRH. The TRH metabolite cyclo (His-Pro) did not influence basal or stimulated pancreatic secretion in vitro. These findings point to a TRH-mediated modulation of exocrine pancreatic secretion at the receptor site.

Effect of injection of thyrotropin-releasing hormone into nucleus accumbens on pain discharges in nucleus parafascicularis of the thalamus in rats

Glass microelectrode recording method was used to investigate the effect of injection of thyrotropin-releasing hormone (TRH) into nucleus accumbens, nucleus amygdalae or nucleus caudatus on unit discharges from pain-excitation neurons (PEN) in nucleus parafascicularis of the thalamus in rats. The results showed that: 1) Injection of TRH into the nucleus accumbens resulted in a significant inhibition of pain discharges from PEN in nucleus parafascicularis, while injection of TRH into nucleus amygdalae, nucleus caudatus exerted no significant effect. 2) Pretreatment with atropine abolished the above-mentioned effect of TRH. 3) Pretreatment with haloperidol also abolished the above-mentioned inhibitory effect of TRH. 4) Pretreatment with naloxone, propranolol or phentolamine did not affect the inhibitory effect of TRH. These results suggested that nucleus accumbens might be a special area in response to TRH and the effect of TRH seems to be involved in both cholinergic M-receptor and dopaminergic receptor.

Thyrotropin-releasing hormone induces opposite effects on Ca2+ channel currents in pituitary cells by two pathways.

Thyrotropin-releasing hormone (TRH) stimulates pituitary secretion by steps involving a cytosolic Ca2+ rise. We examined various pathways of Ca2+ elevation in pituitary GH3 cells. By using the patch clamp technique in the whole-cell configuration and Ba2+ as divalent charge carrier through Ca2+ channels, TRH (1 microM) reversibly reduced the current by about 55%. This hormonal effect was prevented by infusing guanine 5'-[beta-thio]diphosphate (GDP[beta S]) intracellularly but not by pretreating the cell with pertussis toxin (PT). Since PT-insensitive guanine nucleotide-binding regulatory (G) proteins are known to mediate a hormone-stimulated inositol trisphosphate-mediated Ca2+ release from intracellular stores, we assume that the inhibitory effect of TRH on Ba2+ currents through Ca2+ channels is caused by the increased intracellular Ca2+. To prevent a Ca(2+)-release-dependent inhibition of Ca2+ channels, we preincubated GH3 cells in a medium free of divalent charge carriers and measured the Na+ current through Ca2+ channels. When fura-2 was used as indicator for the cytosolic Ca2+, TRH induced a release from intracellular stores only once and had no effect on the intracellular Ca2+ concentration during further applications. In line with this observation, TRH initially reduced the Na+ current through Ca2+ channels but stimulated it during subsequent applications. The stimulation was sensitive to GDP[beta S] and was abolished by pretreatment with PT, suggesting that the stimulatory action of TRH is mediated by a G protein different from the one that functionally couples the receptor to phosphatidylinositol 4,5-bisphosphate hydrolysis. In conclusion, the present data suggest that TRH increases the intracellular Ca2+ concentration by two interacting pathways, that release from intracellular stores causes a secondary blockage of Ca2+ channels, and that, especially with empty intracellular Ca2+ stores, Ca2+ channels are stimulated by a PT-sensitive G protein.

Effect of Intracerebroventricular injection of thyrotropin-releasing hormone on the nociceptive discharges in mesencephalic reticular formation in the rat

Extracellular recording method was used to examine the effect of thyrotropin-releasing hormone (TRH) on 71 unit discharges of pain-excited neurons (PEN) in mesencephalic reticular formation (MRF) in 58 rats. Intracerebroventricular (icv) injection of TRH (10 micrograms/10 micrograms) produced significant decrease of pain discharge rate of PEN. TRH potentiated the inhibitory effect of electroacupuncture (EA) on nociceptive discharges when application of EA at bilateral "Zusanli" was coupled with icv injection of TRH. Both of these inhibiting effects of TRH were completely offset or strikingly decreased by icv preinjection of the cholinergic M-receptor blocker atropine. The results mentioned above and the mechanism of the inhibitory effect of TRH on pain discharges were discussed in this paper.

Neuroanatomic localization of the inhibitory effect of TRH on growth hormone secretion.

The inhibitory effect of centrally administered thyrotropin-releasing hormone (TRH) on the plasma growth hormone (GH) response to GH-releasing hormone (GHRH) in the rat was studied in relation to the anatomic loci involved. Experiments were performed in animals with bilateral electrolytic lesions in the medial preoptic (MPO) area or with anterolateral hypothalamic deafferentation and in sham-operated controls. Blood samples were obtained every 10 to 20 min from and drugs were injected into freely moving animals with indwelling cannulas in the right atrium and lateral cerebral ventricle. In control animals, the plasma GH response to GHRH, 1 microgram iv, was almost completely inhibited by TRH, 1 microgram icv, injected 5 min previously. In animals with either MPO lesions or anterolateral hypothalamic deafferentation in which median eminence somatostatin immunochemical staining was almost completely eliminated, the GH response to GHRH was enhanced and TRH did not exhibit any inhibitory effect. These results, together with the previous observation that the inhibitory effect of TRH is blocked by prior treatment with anti-somatostatin serum, suggest that the effect of TRH is mediated by stimulation of somatostatin-containing neurons in the periventricular nucleus of the MPO area.

Effect of thyrotropin-releasing hormone (TRH) on gastric motility in man

The effect of TRH on gastric antral motor activity was examined in human subjects. Antral motor activity was assessed by balloon-kymography and electromyography (EMG). A balloon and an electrode were introduced into the gastric antrum through 2 channel fiberscope. When TRH was administered iv bolus at a dose of 250 or 500μg, gastric peristalsis was completely inhibited for 5-10min. Time of occurrence of rhythmic contraction during recovery was not modulated by previous TRH injection. When TRH was infused iv at a rate of 4μg/min, gastric peristalsis was inhibited completely for as long as the subjects were receiving TRH. Reinfusion of TRH after a short period of cessation similarly inhibited gastric peristalsis. The inhibitory effect of TRH on gastric motor activity was also confirmed by endoscopy and polysogram of the stomach.These results demonstrate that TRH administered iv exerts a potent inhibitory effect on gastric motor activity in human subjects and that the phenomenon of desentization and/or tachylaxis were not observed. Thus, TRH can be considered a useful adjunct to endoscopic and roentgenographic examinations of the stomach.

Suppression by thyrotropin-releasing hormone (TRH) of growth hormone release induced by arginine and insulin-induced hypoglycemia in man.

Plasma growth hormone (GH) levels were significantly increased following L-arginine (30 g) infusion or insulin (0.1 U/kg body wt)-induced hypoglycemia in normal men. When synthetic thyrotropin-releasing hormone (TRH) (1 mg) was infused intravenously for 150 min, beginning 30 min before arginine or insulin administration, GH responses to arginine and insulin were significantly blunted with a mean (+/- SE) percentage inhibition of 80.1 +/- 8.8% and 30.6 +/- 10.3%, respectively. These results suggest a possible inhibitory effect of TRH on GH secretion in man.