Disease relevance of Trh

• In contrast, basal TRH expression was increased in TR-beta2-null mice to levels seen in hypothyroid wild-type mice and did not change significantly in response to induction of hypothyroidism or T(3) treatment [1].
• The TRH-/- mice also exhibited hyperglycemia, which was accompanied by impaired insulin secretion in response to glucose [2].
• The effect of TRH was observed in cells transfected with expression vectors in which TRH-R cDNA was controlled by cytomegalovirus or Rous sarcoma virus promoters [3].
• Receptor density determines secretory response patterns mediate by inositol lipid-derived second messengers. Comparison of thyrotropin-releasing hormone and carbamylcholine actions in thyroid-stimulating hormone-secreting mouse pituitary tumor cells [4].
• In addition, TRH reduced the sleep and hypothermia produced by thiopental, amobarbital, secobarbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam [5].

Psychiatry related information on Trh

• In the rat, 48 h of food deprivation significantly reduces hypothalamic paraventricular nucleus (PVN) thyrotropin-releasing hormone (TRH) gene expression, anterior pituitary thyrotropin (TSH) gene expression and circulating triiodothyronine (T3) [6].
• It is concluded that TRH and its analogs may be useful in combating some of the withdrawal symptoms in opiate-dependent subjects [7].
• Furthermore, TRH-SR significantly improved the impairment of water maze learning in SAMP8 mice [8].
• These results suggest that TRH-SR may be useful for treatment of age-related emotional disorders and memory disturbance in dementia [8].
• There is considerable evidence linking alcohol consumption, sedation, and thyrotropin-releasing hormone (TRH) in the brain septum [9].

High impact information on Trh

• The ectopically expressed TRHR links to the phosphoinositide pathway, providing a means to regulate liver function with TRH, an extracellular ligand that does not normally affect hepatic function [10].
• Ectopic expression of thyrotropin releasing hormone (TRH) receptors in liver modulates organ function to regulate blood glucose by TRH [10].
• Administration of TRH to these animals activates the phosphoinositide pathway, resulting in a sustained rise in blood glucose [10].
• Small intestine epithelial cells were found to express receptors for thyrotropin-releasing hormone (TRH) and to be a primary source of intestine-derived thyroid-stimulating hormone (TSH) [11].
• These differences are resolved by the finding that administration of the neuropeptide thyrotropin-releasing hormone to adult mice thymectomized as neonates leads to the development of all IEL T cells [12].

Chemical compound and disease context of Trh

• Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia [5].
• Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content [13].
• Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia, but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not [5].
• However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent [13].
• As previously demonstrated, fasting markedly reduced PVN TRH transcripts, pituitary TSB beta transcripts, circulating T3 and body weight [6].

Biological context of Trh

• Binding sites for TRH are present in these tissues, but the TRH receptor (TRH-R) has not been purified from any source [14].
• Finally, transfection of COS-1 cells with this cDNA leads to expression of receptors that bind TRH and chlordiazepoxide with appropriate affinities and that transduce TRH stimulation of inositol phosphate formation [14].
• We present an hypothesis that explains specific regulation of TRH-R mRNA degradation by TRH in GH3 pituitary cells [15].
• These data suggest that TRH specifically enhances the in vitro antibody response via production of immunoreactive TSH [16].
• Alternatively, TRH inhibited PKC activity by reducing the EGF receptor serine/threonine phosphorylation, thereby enhancing tyrosine phosphorylation [17].

Anatomical context of Trh

• Antisense RNA inhibits the TRH response in Xenopus oocytes injected with RNA isolated from normal rat anterior pituitary glands [14].
• Thyrotropin-releasing hormone (TRH) is an important extracellular regulatory molecule that functions as a releasing factor in the anterior pituitary gland and as a neurotransmitter/neuromodulator in the central and peripheral nervous systems [14].
• The activation of the EGF receptor by TRH in multiple circumstances may have important implications for pancreatic beta-cell biology [17].
• Thyrotropin-releasing hormone (TRH) is localized in the brain hypothalamus and stimulates the secretion and synthesis of pituitary thyrotropin (TSH) [18].
• In the present study, we characterized TRH receptors (TRHR) in mouse pancreatic islets and HIT-T15 cells, a hamster clonal beta cell line [19].

Associations of Trh with chemical compounds

• Receptors for thyrotropin-releasing hormone (TRH) are present on mouse pituitary thyrotropic tumor cells [20].
• Incubation with 100 nM TRH and 4 nM T3 caused a significantly greater reduction in the receptor level than either hormone alone [20].
• Injection of sense RNA transcribed in vitro from this cDNA into Xenopus oocytes leads to expression of cell-surface receptors that bind TRH and the competitive antagonist chlordiazepoxide with appropriate affinities and that elicit electrophysiological responses to TRH with the appropriate concentration dependency [14].
• Hydrogen bonding interaction of thyrotropin-releasing hormone (TRH) with transmembrane tyrosine 106 of the TRH receptor [21].
• The affinity of [Phe106]TRH-R for [Pro1]TRH was only 16-fold lower than that for TRH, demonstrating a lack of additivity of the effects of these changes in the receptor and ligand [21].

Physical interactions of Trh

• These data provide compelling evidence that the hydroxyl group of Tyr106 of the TRH-R binds the TRH pyroglutamyl carbonyl group [21].
• Thyrotropin-releasing hormone binding to the mouse pituitary receptor does not involve ionic interactions. A model for neutral peptide binding to G protein-coupled receptors [22].

Regulatory relationships of Trh

• This enhancement effect by TRH was specifically blocked by rabbit antisera to the TSH-beta subunit, whereas addition of normal rabbit sera had no effect [16].
• Since TRH and PMA down-regulate TRH-R mRNA in GH3 cells, posttranscriptional regulation of TRH-R mRNA is a cell-type specific process [3].
• At 30 min, endogenous beta-arrestins reduced TRH-stimulated inositol phosphate production by 48% (beta-arrestin-1), 71% (beta-arrestin-2), and 84% (beta-arrestins-1 and -2) [23].
• Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production [24].

Other interactions of Trh

• Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons [1].
• However, the suppression of TRH mRNA expression in response to leptin reduction during fasting was preserved in TR-beta2-null mice [1].
• Thus TR-beta2 is the key TR isoform responsible for T(3)-mediated negative-feedback regulation by hypophysiotropic TRH neurons [1].
• TRH affected RNase activity in a biphasic manner with rapid stimulation (by 10 min) followed by a decrease to a rate slower than in control lysates within 6 h [15].
• As a result of these studies, experiments were designed to examine the possible immunoregulatory function of thyrotropin-releasing hormone (TRH) on the in vitro antibody response to the T cell-independent Ag BA-TNP [16].

Analytical, diagnostic and therapeutic context of Trh

• Effect of thyrotropin-releasing hormone on the carbohydrate structure of secreted mouse thyrotropin. Analysis by lectin affinity chromatography [25].
• Functional thyrotropin-releasing hormone (TRH) receptors have been expressed in Xenopus laevis oocytes following the microinjection of total and poly(A)+ RNA from GH3 rat anterior pituitary tumour cells [26].
• We have also demonstrated the benefits of the prodrug approach on the pharmacokinetics and brain uptake/retention of pyridinium-containing TRH analogues (measured by in vivo microdialysis sampling) upon systemic administration [27].
• Thyrotropin or L-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital [5].
• To examine the expression of potential TRH regulatory components, we simultaneously amplified, by semi-quantitative multiplex PCR system, nine key genes from < or = 100 ng total RNA from two brain areas (hypothalamus and cortex) under different thyroid states [28].

References