Disease relevance of Trhr

• Rapid temperature-dependent transformation of the thyrotropin-releasing hormone-receptor complex in rat pituitary tumor cells [1].
• In contrast to its lack of effect on TRH receptor binding, 3-h pertussis toxin treatment decreased agonist affinity of the mu-opiate receptor and abolished the ability of GTP gamma S to shift the affinity of the mu-opiate receptor for its agonist [2].
• We have previously demonstrated the existence of intact TRH receptor mRNA in GH-secreting adenoma [3].
• Hemorrhagic shock significantly decreased TRH receptor binding in the septum and hindbrain [4].
• TRH receptor agonists ameliorate 3-acetylpyridine-induced ataxia through NMDA receptors in rats [5].

High impact information on Trhr

• In GH3 cells, TRH caused a rapid decrease in TRH-R mRNA activity to 15 percent of control within 3 hours [6].
• The mechanism of TRH-R downregulation was studied by monitoring TRH-evoked depolarizing currents in Xenopus oocytes injected with GH3 cell RNA as a bioassay for TRH-R messenger RNA (mRNA) activity [6].
• Decreased TRH receptor mRNA activity precedes homologous downregulation: assay in oocytes [6].
• The dissociation of these actions suggests that there are separate mechanisms involved in coupling TRH-receptor complexes to stimulation of PtdIns(4,5)P2 and PtdIns hydrolysis in GH3 cells [7].
• Stimulation of GTPase depended on occupancy of the TRH receptor; half-maximal increases in GTPase activity required 46 nM TRH and 25 nM [N3-methyl-His]TRH, but the TRH free acid was inactive [8].

Chemical compound and disease context of Trhr

• In contrast to the lack of effect of pertussis toxin on the TRH receptor system, treatment of 7315c cells with pertussis toxin for 3 h or longer completely abolished the ability of morphine, an opiate agonist, to inhibit either adenylate cyclase activity or prolactin release [9].
• Treatment of cells with pertussis toxin did not alter the affinity or concentration of TRH receptors, or the sensitivity of the TRH receptor to inhibition by guanine nucleotides [10].
• The increased pituitary TRH receptor content, response to TRH administration and the fact that regulation at the level of the pituitary is not affected in the pyridoxine-deficient rat indicates a hypothalamic origin for the hypothyroidism of the pyridoxine-deficient rat [11].

Biological context of Trhr

• Constitutive and agonist-dependent homo-oligomerization of the thyrotropin-releasing hormone receptor. Detection in living cells using bioluminescence resonance energy transfer [12].
• Two isoforms of the thyrotropin-releasing hormone receptor generated by alternative splicing have indistinguishable functional properties [13].
• Furthermore, the perfect colinearity between genomic DNA and TRH-R(412) cDNA demonstrates that no other introns are present within the coding region of the TRH receptor gene [13].
• Using the polymerase chain reaction with degenerate primers and pools of cloned cDNAs from a GH4C1 cDNA library, a fragment sharing high similarity to the mouse thyrotrope TRHR (mTRHR) was identified [14].
• These cell lines are good models for understanding the mechanisms by which the GnRH receptor is coupled to second messenger systems and for comparing these mechanisms with TRH-receptor coupling in the same cell [15].

Anatomical context of Trhr

• To compare responses to TRH and GnRH directly within one cell type, we have stably transfected the rat pituitary GH3 lactotrope cell line, which expresses the endogenous TRH receptor, with an expression vector containing rat GnRH receptor cDNA [16].
• Treatment of GH3 cells with E2 increased TRH receptor mRNA activity, as assessed in the oocyte expression system; the E2 effect became apparent after 3 h of treatment and reached a maximum (3- to 4-fold) between 6-72 h after addition [17].
• This truncated TRH-R mRNA, along with the longer receptor form, was found to be expressed throughout the rat pituitary gland and brain [18].
• A truncated isoform of the thyrotropin-releasing hormone receptor is expressed in the rat central nervous system as well as in the pituitary gland [18].
• RESULTS: This study demonstrates that TRH receptor 1 (TRHR1) mRNA expression is up-regulated in the pituitary and in discrete nuclei of the hypothalamus in lactating rats, while proTRH mRNA expression levels are increased only in the hypothalamus [19].

Associations of Trhr with chemical compounds

• Estradiol transcriptionally and posttranscriptionally up-regulates thyrotropin-releasing hormone receptor messenger ribonucleic acid in rat pituitary cells [17].
• In GH3 cells, however, no significant change of TRH-R mRNA level was observed between cultures treated with triiodothyronine (T3, 10(-9) and 10(-7) M) and the untreated group [20].
• These findings suggest that a guanine nucleotide-binding regulatory protein is involved in coupling the TRH receptor to a phospholipase C that hydrolyzes PtdIns(4,5)P2 [21].
• GTP gamma S (0.1 microM) decreased the affinity of the TRH receptor for [3H]Me-TRH from 2 to 100 nM [2].
• Specifically, the Cys residues at positions 335 and 337 are important for preventing constitutive TRHR internalization, because a mutant HA-C335S/C337S receptor was sequestered constitutively [22].

Physical interactions of Trhr

• Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells) [23].

Regulatory relationships of Trhr

• This suggested that the affinity of TRH ligands for the TRH receptor influences the activation of EGF receptor phosphorylation in betaTC-6 cells [24].
• Thus, we conclude that the suckling-induced increase in mammotrope responsiveness to TRH is regulated subsequent to TRH receptor activation [25].
• In parallel experiments prolactin treatment during diestrus failed to influence TRH receptor levels in both tissues compared to vehicle-treated rats [26].

Other interactions of Trhr

• At this stage, no effects were observed on the transcript levels of either the TRH receptor or TSH beta [27].
• We describe here the effects of thyroid hormones on the transcript levels of the TRH receptor, the TRH-degrading ectoenzyme, and TSH in rat pituitary, as revealed by Northern blot analysis [27].
• Transcriptional down-regulation by epidermal growth factor of TRH receptor mRNA in rat pituitary cells [28].
• Northern blot analyses and binding studies revealed that EGF reduced both TRH binding and TRH-R mRNA levels in a dose- and time-dependent manner, while no significant changes were observed in beta-actin mRNA levels [28].
• Bromocryptine (10(-8) M), a D2 dopamine receptor agonist, or somatostatin (10(-6) M) stimulated enzyme activity and blocked the inhibitory effect of [3-Me-His2]-TRH, a TRH receptor agonist [29].

Analytical, diagnostic and therapeutic context of Trhr

• In this report, we investigated whether and how E2 alters TRH receptor expression at the mRNA level using the oocyte mRNA expression system, Northern blot analysis, and nuclear run-on assay [17].
• Molecular cloning of a complementary deoxyribonucleic acid encoding the thyrotropin-releasing hormone receptor and regulation of its messenger ribonucleic acid in rat GH cells [14].
• In-situ hybridization in the rat anterior pituitary revealed a heterogeneous distribution of label, a characteristic pattern of TRH-R expression [30].
• Using the reverse transcription-polymerase chain reaction (RT-PCR), a cDNA encoding the entire rat thyrotropin-releasing hormone receptor (TRH-R) was isolated from normal rat pituitary gland mRNA [18].
• The similarity of dose-response curves and time-courses for loss of the two G-proteins indicates that the long isoform of the rat TRH receptor does not functionally select between these two transducer proteins [31].

References