scholarly journals Thyrotropin-Releasing Hormone (TRH) Analogues That Exhibit Selectivity to TRH Receptor Subtype 2.

2006 ◽  
Vol 49 (17) ◽  
pp. 5387-5387
Author(s):  
Navneet Kaur ◽  
Xinping Lu ◽  
Marvin C. Gershengorn ◽  
Rahul Jain
Keyword(s):  
Thyrotropin Releasing Hormone ◽  
Receptor Subtype ◽  
Releasing Hormone ◽  
Trh Analogues ◽  
Trh Receptor

Thyrotropin-Releasing Hormone (TRH) Analogues That Exhibit Selectivity to TRH Receptor Subtype 2

2005 ◽  
Vol 48 (19) ◽  
pp. 6162-6165 ◽  
Author(s):  
Navneet Kaur ◽  
Xinping Lu ◽  
Marvin C. Gershengorn ◽  
Rahul Jain
Keyword(s):  
Thyrotropin Releasing Hormone ◽  
Receptor Subtype ◽  
Releasing Hormone ◽  
Trh Analogues ◽  
Trh Receptor

scholarly journals Synthesis and characterization of a high-affinity photoactivatable analogue of thyrotropin-releasing hormone

1992 ◽  
Vol 281 (1) ◽  
pp. 179-184
Author(s):  
K D Brady ◽  
A H Tashjian
Keyword(s):  
Thyrotropin Releasing Hormone ◽  
British Library ◽  
Releasing Hormone ◽  
High Affinity ◽  
Sds Page ◽  
Rat Pituitary ◽  
Single Polypeptide ◽  
Trh Analogues ◽  
Trh Receptor

An analogue of thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2), i.e. pGlu-His-ProNH-(CH2)6-(4-azidosalicylamide) (TRH-ASA), has been synthesized and, in a radioiodinated form (TRH-IASA), characterized and used as a photoaffinity reagent to label the TRH receptor on rat pituitary GH4C1 cells. TRH-IASA bound to GH4C1 cells with high affinity (Kd = 8 nM), comparable with that of TRH binding. The binding of TRH-IASA was competitive with binding of TRH, two TRH analogues and a TRH receptor antagonist, chlordiazepoxide. TRH-IASA did not bind to or label GH12C1 cells, which lack functional TRH receptors. Labelling of GH4C1 cells with TRH-IASA followed by SDS/PAGE and autoradiography of membrane proteins demonstrated labelling of a single polypeptide which ran as a diffuse band between 71 and 91 kDa, centred at 76 kDa. No change in this labelling pattern was observed as a function of the length of time (between 5 min and 2 h) that GH4C1 cells were incubated with 3 nM-TRH-IASA. Using either a very short (5 s) photolysis interval or low TRH-IASA concentrations, only the 76 kDa band was labelled. Minor bands appeared only after extended photolysis and use of high TRH-IASA concentrations. We conclude that the TRH receptor from rat pituitary GH4C1 cells is a single peptide with an apparent molecular mass of 76 kDa. Details of the chemical synthesis of TRH-ASA are given in Supplementary Publication SUP 50167 (5 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1992) 281, 5.

Expression of Thyrotropin-Releasing Hormone (TRH) receptor subtype 1 in mouse pancreatic islets and HIT-T15, an insulin-secreting clonal β cell line

Life Sciences ◽  
2000 ◽  
Vol 66 (12) ◽  
pp. 1119-1125 ◽  
Author(s):  
Masanobu Yamada ◽  
Nobuyuki Shibusawa ◽  
Tetsu Hashida ◽  
Atsushi Ozawa ◽  
Tsuyoshi Monden ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Cell Line ◽  
Thyrotropin Releasing Hormone ◽  
Receptor Subtype ◽  
Β Cell ◽  
Releasing Hormone ◽  
Mouse Pancreatic Islets ◽  
Trh Receptor

1,25-Dihydroxyvitamin D3-induced upregulation of the thyrotropin-releasing hormone receptor in clonal rat pituitary GH3 cells

1995 ◽  
Vol 147 (3) ◽  
pp. 397-404 ◽  
Author(s):  
L M Atley ◽  
N Lefroy ◽  
J D Wark
Keyword(s):  
Vitamin D ◽  
Fold Increase ◽  
Thyrotropin Releasing Hormone ◽  
Gh3 Cells ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Hormone Production ◽  
Releasing Hormone ◽  
Rat Pituitary ◽  
Trh Receptor

Abstract 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is active in primary dispersed and clonal pituitary cells where it stimulates pituitary hormone production and agonist-induced hormone release. We have studied the effect of 1,25-(OH)2D3 on thyrotropin-releasing hormone (TRH) binding in clonal rat pituitary tumour (GH3) cells. Compared with vehicle-treated cells, 1,25-(OH)2D3 (10 nmol/l) increased specific [3H]MeTRH binding by 26% at 8 h, 38% at 16 h, 35% at 24 h and reached a maximum at 48 h (90%). In dose–response experiments, specific [3H]MeTRH binding increased with 1,25-(OH)2D3 concentration and reached a maximum at 10 nmol/l. Half-maximal binding occurred at 0·5 nmol 1,25-(OH)2D3/l. The vitamin D metabolite, 25-OH D3, increased [3H]MeTRH binding but was 1000-fold less potent than 1,25-(OH)2D3. In equilibrium binding assays, treatment with 10 nmol 1,25-(OH)2D3/l for 48 h increased the maximum binding from 67·4 ± 8·8 fmol/mg protein in vehicle-treated cells to 96·7 ± 12·4 fmol/mg protein in treated cells. There was no difference in apparent Kd (1·08 ± 0·10 nmol/l for 1,25-(OH)2D3-treated and 0·97 ± 0·11 nmol/l for vehicle-treated cells). Molecular investigations revealed that 10 nmol 1,25-(OH)2D3/l for 24 h caused an 8-fold increase in TRH receptor-specific mRNA. Actinomycin D (2 μg/ml, 6 h) abrogated the 1,25-(OH)2D3-induced increase in [3H]MeTRH binding. Cortisol also increased [3H]MeTRH binding but showed no additivity or synergism with 1,25-(OH)2D3. TRH-stimulated prolactin release was not enhanced by 1,25-(OH)2D3. We conclude that the active vitamin D metabolite, 1,25-(OH)2D3, caused a time- and dose-dependent increase in [3H]MeTRH binding. The effect was vitamin D metabolite-specific and resulted from an upregulation of the TRH receptor. Further studies are needed to determine the functional significance of this novel finding. Journal of Endocrinology (1995) 147, 397–404

scholarly journals The Antagonist pGlu-βGlu-Pro-NH2 Binds to an Allosteric Site of the Thyrotropin-Releasing Hormone Receptor

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5397
Author(s):  
Daniel L. De La Cruz ◽  
Laszlo Prokai ◽  
Katalin Prokai-Tatrai
Keyword(s):  
Binding Site ◽  
Homology Model ◽  
Thyrotropin Releasing Hormone ◽  
Allosteric Site ◽  
Releasing Hormone ◽  
Surface Recognition ◽  
Extracellular Loops ◽  
Binding Pockets ◽  
Central Actions ◽  
Trh Receptor

After we identified pGlu-βGlu-Pro-NH2 as the first functional antagonist of the cholinergic central actions of the thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2), we became interested in finding the receptor-associated mechanism responsible for this antagonism. By utilizing a human TRH receptor (hTRH-R) homology model, we first refined the active binding site within the transmembrane bundle of this receptor to enhance TRH’s binding affinity. However, this binding site did not accommodate the TRH antagonist. This prompted us to consider a potential allosteric binding site in the extracellular domain (ECD). Searches for ECD binding pockets prompted a remodeling of the extracellular loops and the N-terminus. We found that different trajectories of ECDs produced novel binding cavities that were then systematically probed with TRH, as well as its antagonist. This led us to establish not only a surface-recognition binding site for TRH, but also an allosteric site that exhibited a selective and high-affinity binding for pGlu-βGlu-Pro-NH2. The allosteric binding of this TRH antagonist is more robust than TRH’s binding to its own active site. The findings reported here may shed light on the mechanisms and the multimodal roles by which the ECD of a TRH receptor is involved in agonist and/or antagonist actions.

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