, Jackson 1989 ) and characterized the Trh gene ( Lee et al . 1989 ). The Trh -gene proximal promoter contains response elements (RE) to transcription factors whose binding was revealed by chromatin immunoprecipitation assays; for example, receptors for
Patricia Joseph-Bravo, Lorraine Jaimes-Hoy, Rosa-María Uribe, and Jean-Louis Charli
Bert De Groef, Sylvia V H Grommen, and Veerle M Darras
secretion ( De Groef et al. 2003 b ). The stimulating effects of TRH on thyrotropes are mediated through the type 1 TRH receptor (TRH-R1) ( De Groef et al. 2003 a ). Changes in the sensitivity of the thyrotropes to the above
P C Lisboa, E de Oliveira, A C Manhães, A P Santos-Silva, C R Pinheiro, V Younes-Rapozo, L C Faustino, T M Ortiga-Carvalho, and E G Moura
& Seitz 1994 , St Germain et al . 2009 ). Most of actions of TH occur through the nuclear TH receptors (TR), which are encoded by two distinct genes, TRα and TRβ, located on mouse chromosomes 11 and 14. The molecular mechanism of TH action involves TR
regulate TRH gene expression via activation of intracellular signal-transducer-and-activator-of transcription 3 (STAT-3) proteins in TRH neurons, with evidence that the STAT-3 binding site on the leptin receptor is also required for the effect on TRH
Patricia C Lisboa, Ellen P S Conceição, Elaine de Oliveira, and Egberto G Moura
understanding regarding the degree of hypothyroidism previously reported in EO animal models. Because circulating thyrotropin (TSH) was unaltered in adult small litter (SL) rats, we evaluated the thyrotropin release hormone (TRH) in the hypothalamus, the TSH in
F Aréchiga-Ceballos, E Alvarez-Salas, G Matamoros-Trejo, M I Amaya, C García-Luna, and P de Gortari
thyroxine (T 4 ) – as well as their degrading effects on fuel reservoirs. TRH is the hypophysiotropic factor that controls HPT axis function. This peptide is synthesized in the medial PVN (mPVN) of the hypothalamus and released into the portal blood to
T V Novoselova, R Larder, D Rimmington, C Lelliott, E H Wynn, R J Gorrigan, P H Tate, L Guasti, The Sanger Mouse Genetics Project, S O’Rahilly, A J L Clark, D W Logan, A P Coll, and L F Chan
Introduction Melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are a recently identified class of small, single-pass transmembrane domain accessory proteins ( Chan et al . 2009 , Novoselova et al . 2013 ). Both MRAP and
LG Luo and N Yano
Thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide, is expressed in pancreatic islets at peak levels during the late gestation and early neonate period. TRH increases insulin production in cultured beta-cells, suggesting that it might play a role in regulating pancreatic beta-cell function. However, there is limited information on TRH receptor expression in the pancreas. The aim of the present study was to explore the distribution of the TRH receptor in the pancreas and its function in pancreatic beta-cells. TRH receptor type 1 (TRHR1) gene expression was detected by RT-PCR and verified by Northern blotting and immunoblotting in the beta-cell lines, INS-1 and betaTC-6, and the rat pancreatic organ. The absence of TRH receptor type 2 expression in the tissue and cells indicated the tissue specificity of TRH receptor expression in the pancreas. The TRHR1 signals (detected by in situ hybridization) were distributed not only in islets but also in the surrounding areas of the pancreatic ductal and vasal epithelia. The apparent dissociation constant value for the affinity of [(3)H]3-methyl-histidine TRH (MeTRH) is 4.19 in INS-1 and 3.09 nM in betaTC-6. In addition, TRH induced epidermal growth factor (EGF) receptor phosphorylation with a half-maximum concentration of approximately 50 nM, whereas the high affinity analogue of TRH, MeTRH, was 1 nM. This suggested that the affinity of TRH ligands for the TRH receptor influences the activation of EGF receptor phosphorylation in betaTC-6 cells. Our observations suggested that the biological role of TRH in pancreatic beta-cells is via the activation of TRHR1. Further research is required to identify the role of TRHR1 in the pancreas aside from the islets.
BH Duvilanski, D Pisera, A Seilicovich, M del Carmen Diaz, M Lasaga, E Isovich, and MO Velardez
Substance P (SP) may participate as a paracrine and/or autocrine factor in the regulation of anterior pituitary function. This project studied the effect of TRH on SP content and release from anterior pituitary and the role of SP in TRH-induced prolactin release. TRH (10(-7) M), but not vasoactive intestinal polypeptide (VIP), increased immunoreactive-SP (ir-SP) content and release from male rat anterior pituitary in vitro. An anti-prolactin serum also increased ir-SP release and content. In order to determine whether intrapituitary SP participates in TRH-induced prolactin release, anterior pituitaries were incubated with TRH (10(-7) M) and either WIN 62,577, a specific antagonist of the NK1 receptor, or a specific anti-SP serum. Both WIN 62,577 (10(-8) and 10(-7) M) and the anti-SP serum (1:250) blocked TRH-induced prolactin release. In order to study the interaction between TRH and SP on prolactin release, anterior pituitaries were incubated with either TRH (10(-7) M) or SP, or with both peptides. SP (10(-7) and 10(-6) M) by itself stimulated prolactin release. While 10(-7) M SP did not modify the TRH effect, 10(-6) M SP reduced TRH-stimulated prolactin release. SP (10(-5) M) alone failed to stimulate prolactin release and markedly decreased TRH-induced prolactin release. The present study shows that TRH stimulates ir-SP release and increases ir-SP content in the anterior pituitary. Our data also suggest that SP may act as a modulator of TRH effect on prolactin secretion by a paracrine mechanism.
KL Geris, B de Groef, SP Rohrer, S Geelissen, ER Kuhn, and VM Darras
Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resistance and reproduction. Five SRIH receptors (sstr1-5) have been identified in mammals, where they are expressed in both the brain and peripheral tIssues. To study the specific function of each receptor subtype, specific agonists (ag1-5) have been synthesized. The high degree of homology between mammalian and avian SRIH receptors suggests that these agonists might also be used in chickens. In this paper we describe two in vitro protocols (static incubation and perifusion system) to identify the SRIH receptors controlling the secretion of GH and TSH from the chicken pituitary. We found that basal GH or TSH secretion were never affected when SRIH or an agonist (1 microM) were added. SRIH diminished the GH as well as the TSH response to TSH-releasing hormone (TRH; 100 nM) in both systems. Our results have indicated that the SRIH actions at the level of the pituitary are regulated through specific receptor subtypes. In both the static and flow incubations, ag2 lowered the GH response to TRH, whereas stimulated TSH release was diminished by both ag2 and ag5. Ag3 and ag4 tended to increase rather than decrease the responsiveness of both pituitary cell types to TRH in perifusion studies. Our data have indicated that SRIH inhibits chicken pituitary function through sstr2 and sstr5. Only sstr2 seems to be involved in the control of chicken GH release, whereas both sstr2 and sstr5 inhibit induced GH secretion in mammals. The possible stimulatory action of ag3 and ag4 may point towards a species-specific function of sstr3 and sstr4.