Disease relevance of Trh

• Regulation of the mitogen-activated protein (MAP) kinase by thyrotropin-releasing hormone (TRH) in GH3 rat pituitary tumor cells was investigated [1].
• I.v. injected TRH enhanced somewhat FT3 concentration in blood plasma of euhydrated animals but diminished FT4 plasma level during dehydration [2].
• Male rats (Holtzman strain, 240-270 g body weight) injected with progressive doses of TRH (100, 200 and 400 ng) at 5-day intervals were compared with the control state (injection of artificial cerebrospinal fluid, CSF) [3].
• CONCLUSIONS: Taken together, these results indicate that TRH is specifically induced in the heart after MI and that it can increase cardiac performance in rats with ischemic cardiomyopathy [4].
• BACKGROUND: We reported previously that left ventricular gene expression for thyrotropin-releasing hormone (TRH) precursor was increased in rats with heart failure 8 weeks after myocardial infarction (MI) and that early ACE inhibition tended to cause further myocardial induction of this gene [4].

Psychiatry related information on Trh

• The results show that injection of TRH into the NAS, but not the injection of LHRH or CRH, selectively increases face grooming without affecting other subcategories of grooming at the doses used, and appears to link this peptide with the neural substrate of stereotyped behavior [3].
• Food deprivation for 3 days increased levels by 35% and refeeding completely normalized TRH content again [5].
• In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia [6].
• TRH present in extrahypothalamic brain areas has been postulated to serve as a neuromodulator and levels of this peptide increase in amygdala, hippocampus and cortex after electrical stimulation (kindling or electroshock) [7].
• Thyrotropin-releasing hormone and dementia [8].

High impact information on Trh

• Adenohypophyseal degradation of thyrotropin releasing hormone regulated by thyroid hormones [9].
• Conversion of PtdIns to polyphosphoinositides and TRH (and GTP)-activated phosphoinositide hydrolysis are known to occur in plasma membrane isolated from GH3 cells [10].
• GH3 rat pituitary tumour cells are an excellent model system to study stimulation of phosphoinositide metabolism by thyrotropin-releasing hormone (TRH) [10].
• We report here that thyrotropin-releasing hormone (TRH) acts within the CNS to elicit a vagus-dependent stimulation of gastric acid secretion [11].
• This report describes studies with nerve endings isolated from the rat hypothalamus in which dopamine at higher concentrations than those used previously has been found to stimulate the degradation of LH-RH but not thyrotropin releasing hormone (TRH) [12].

Chemical compound and disease context of Trh

• An analogue of creatine increases TRH-stimulated prolactin secretion and phosphoinositide hydrolysis in rat pituitary tumor cells [13].
• In most cells, estradiol and TRH led to an increase in the number and prominence of microvilli and blebs, whereas CB-154 treatment resulted in a slightly decreased number of microvilli and an increased occurrence of membrane foldings [14].
• 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 [15].
• Induction of hyperthyroidism with thyroxine increased levels of TRH in the PP by 20%, whereas in methimazole-treated, hypothyroid rats the content decreased by 25% versus untreated, euthyroid controls [5].
• Pertussis toxin (1 nM, 4 h) attenuated both the basal and TRH-stimulated IP3 production, but this effect was omitted by calcitriol pretreatment [16].

Biological context of Trh

• In contrast, inhibitors of the slow calcium channel exert minimal effects on TRH-stimulated prolactin gene expression, suggesting that calcium influx through membrane channels is not crucial for the observed nuclear actions of TRH [17].
• Thyrotropin-releasing hormone stimulates MAP kinase activity in GH3 cells by divergent pathways. Evidence of a role for early tyrosine phosphorylation [1].
• In stable clones overexpressing nPKC epsilon, immunocytofluorescence and immunoblot experiments indicated that TRH causes the rapid translocation and down-regulation of an appreciable fraction of nPKC epsilon [18].
• Thyrotropin-releasing hormone and epidermal growth factor regulate iron-regulatory protein binding in pituitary cells via protein kinase C-dependent and -independent signaling pathways [19].
• Treatment with a high dosage (2 micrograms) of TRH induced a sixfold rise in plasma TSH during both phases of gestation [20].

Anatomical context of Trh

• Interestingly, ferritin protein levels were regulated similarly by TRH in both cell lines [19].
• Thyroidectomy induces Fos-like immunoreactivity within thyrotropin-releasing hormone-expressing neurons located in the paraventricular nucleus of the adult rat hypothalamus [21].
• Thyroid stimulating hormone and prolactin secretion: reduced sensitivity to TRH-stimulated prolactin release after midpregnancy in rats [20].
• Intracisternal (i.c.) thyrotropin-releasing hormone (TRH) increases contractility, gastric acid secretion and the incidence of erosion formation [22].
• Since pentobarbital and morphine-induced hormonal changes are probably exerted through a central nervous system depressant action, these data indicate that TRH can influence brain activity through an extrapituitary mechanism [23].

Associations of Trh with chemical compounds

• The biphasic nature of TRH action on [Ca2+]i parallels the biphasic actions of TRH on 45Ca2+ fluxes and the biphasic release of PRL by GH cells in suspension [24].
• TRH stimulated the tyrosine phosphorylation of the 52-kDa Shc protein, although neither phorbol esters nor the calcium ionophore A23187 had any effect, indicating that this effect of TRH was not dependent on PKC [1].
• The TRH-induced spike phase was attenuated but not abolished by prior addition of EGTA, while the plateau phase was eliminated by EGTA [24].
• TRH-dependent cyclic AMP accumulation was markedly potentiated by forskolin in Ca2+-restored, but not in Ca2+-depleted, cell preparations [25].
• Exposure of GH3 cells preloaded with 45Ca to TRH, PGE1, EGF, PMA, or VIP resulted in losses of cell-associated 45Ca [25].

Physical interactions of Trh

• CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats [26].
• TRH stimulation appears to be coupled to PRL secretion, at least in part, by elevation of the concentration of Ca2+ free in the cytoplasm [( Ca2+]i) [27].
• Regulation of thyrotropin-releasing hormone binding by monovalent cations and guanyl nucleotides [28].
• Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme [29].

Enzymatic interactions of Trh

• Thyrotropin-releasing hormone-degrading ectoenzyme is a member of the M1 family of Zn-dependent aminopeptidases and catalyzes the degradation of thyrotropin-releasing hormone (TRH; Glp-His-Pro-NH2) [30].

Regulatory relationships of Trh

• Thyrotropin-releasing hormone-induced spike and plateau in cytosolic free Ca2+ concentrations in pituitary cells. Relation to prolactin release [24].
• GH4 pituitary cell variants selected as nonresponsive to thyrotropin-releasing hormone-enhanced substratum adhesion are nonresponsive to epidermal growth factor: evidence for a common signaling defect [31].
• METHODS AND RESULTS: Here, we show that after MI, the expression of pro-TRH is induced in the heart coordinately with the protease PC1, an important enzyme in TRH biosynthesis [4].
• Taken together, the data suggest that Fos-like IR is induced within TRH-expressing neurons in the pPVN as a consequence of decreasing levels of circulating thyroid hormone (TH) [21].
• The TRH-induced increases in c-fos and beta-actin mRNA may play a role in the secretory response [32].

Other interactions of Trh

• Nuclear ER-alpha ir was found in a population of thyrotropin-releasing hormone (TRH)-expressing neurons in the PVN (5.93% +/- 1.20% SEM), but not in any other identified cell phenotype of the PVN and SON [33].
• Low levels of corticotropin-releasing hormone neurons also expressed ER-beta ir in the PVN (12.57% +/- 1.99%), but there was no ER-beta colocalization with TRH [33].
• Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way [34].
• Thyrotropin-releasing hormone increases the levels of c-fos and beta-actin mRNA in GH3/B6 pituitary tumor cells [32].
• The TRH effects on N-myc mRNA levels were less consistent [32].

Analytical, diagnostic and therapeutic context of Trh

• A significant correlation between numbers of Fos-like IR cells in the pPVN and plasma TSH concentration following thyroidectomy was also observed, suggesting that plasma levels of TSH correlate directly with the number of activated TRH-containing neurons located in the pPVN [21].
• TRH and AP hormones including GH, prolactin (PRL), luteinizing hormone (LH) and thyrotropin (TSH) were measured by RIA, proTRH mRNA was determined by in situ hybridization using a full-length riboprobe followed by quantification with a computer-assisted image analysis system [35].
• Gel filtration of BHE on the Sephadex G-100 column yielded two peaks of PRA distinct from TRH, VIP and END [36].
• The proteins modified by TRH treatment were present in low amounts in the cell; they were not detectable by silver staining of the gels, except for protein 1 (Mr = 80,000) whose TRH-induced conversion from its unphosphorylated to its more acidic phosphorylated form was observed directly on silver-stained gels [37].
• To determine whether CART and TRH interact in the regulation of anterior pituitary function, we have studied the effects of CART on TRH-induced release of TSH and prolactin in anterior pituitary cell cultures, and the effects of hypo- and hyperthyroidism on CART mRNA in the PVN [38].

References