A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor†

Biochemistry ◽  
1996 ◽  
Vol 35 (24) ◽  
pp. 7651-7663 ◽  
Author(s):  
Liisa J. Laakkonen ◽  
Frank Guarnieri ◽  
Jeffrey H. Perlman ◽  
Marvin C. Gershengorn ◽  
Roman Osman
Keyword(s):  
Monte Carlo ◽  
Receptor Binding ◽  
Mixed Mode ◽  
Stochastic Dynamics ◽  
Binding Pocket ◽  
Thyrotropin Releasing Hormone ◽  
Refined Model ◽  
Releasing Hormone ◽  
Dynamics Simulations ◽  
Trh Receptor

Molecular and cellular biology of thyrotropin-releasing hormone receptors

1996 ◽  
Vol 76 (1) ◽  
pp. 175-191 ◽  
Author(s):  
M. C. Gershengorn ◽  
R. Osman
Keyword(s):  
Hormone Receptors ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Amino Acid Sequences ◽  
Thyrotropin Releasing Hormone ◽  
Cellular Biology ◽  
Dimensional Structure ◽  
Releasing Hormone ◽  
G Protein Coupled ◽  
Trh Receptor

Thyrotropin-releasing hormone (TRH) receptor (TRH-R) complementary DNAs have been cloned from several species. The deduced amino acid sequences are compatible with TRH-R being a seven-transmembrane-spanning G protein-coupled receptor. These complementary DNAs and reagents derived from them have permitted detailed study of TRH-R biology at the molecular and cellular levels. Studies that have been performed since 1990 are reviewed in this article under the following headings: TRH-R gene, tissue distribution of TRH-R, primary structure of TRH-Rs, three-dimensional structure of the TRH-R binding pocket, TRH-R and G proteins, TRH-R activation, TRH desensitization, TRH-R endocytosis, and regulation of TRH-R number. It is evident that many new insights into the structure, function, and regulation of TRH-Rs have been gained in the last several years but that our understanding of these processes is incomplete. We look forward to even greater progress in the future.

Discrete regional distributions of thyrotropin releasing hormone (TRH) receptor binding in monkey central nervous system

1981 ◽  
Vol 205 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Norio Ogawa ◽  
Yasuhide Yamawaki ◽  
Hiroo Kuroda ◽  
Tadashi Ofuji ◽  
Eiko Itoga ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Receptor Binding ◽  
Thyrotropin Releasing Hormone ◽  
Releasing Hormone ◽  
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

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