Growth-hormone-releasing hormone receptor explained

The growth-hormone-releasing hormone receptor (GHRHR) is a G-protein-coupled receptor that binds growth hormone-releasing hormone. The GHRHR activates a Gs protein that causes a cascade of cAMP via adenylate cyclase.^[1] GHRHR is distinct from the growth hormone secretagogue receptor (also known as the ghrelin receptor), where growth hormone releasing peptides act to release growth hormone.

Function

This gene, expressed in the pituitary, encodes a receptor for growth-hormone-releasing hormone. Binding of this hormone to the receptor leads to synthesis and release of growth hormone. Mutations in this gene have been associated with isolated growth-hormone deficiency (IGHD), also known as Dwarfism of Sindh, a disorder characterized by short stature. Many alternate transcriptional splice variants encoding different isoforms have been described, but only two have been characterized to date.^[2]

Ligands

Agonists

• CJC-1295
• Dumorelin
• GHRH (somatorelin)
• Rismorelin
• Sermorelin
• Tesamorelin

Antagonists

• MZ-5-156^{[3] [4]}

Further reading

• Gaylinn BD . Molecular and cell biology of the growth hormone-releasing hormone receptor . Growth Hormone & IGF Research . 9 Suppl A . 37–44 . Apr 1999 . 10429879 . 10.1016/S1096-6374(99)80008-2 .
• Lin-Su K, Wajnrajch MP . Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor . Reviews in Endocrine & Metabolic Disorders . 3 . 4 . 313–23 . Dec 2002 . 12424433 . 10.1023/A:1020949507265 . 6263928 .
• Mayo KE . Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone . Molecular Endocrinology . 6 . 10 . 1734–44 . Oct 1992 . 10.1210/mend.6.10.1333056 . 1333056 . free .
• Squire J, Zhou A, Hassel BA, Nie H, Silverman RH . Localization of the interferon-induced, 2-5A-dependent RNase gene (RNS4) to human chromosome 1q25 . Genomics . 19 . 1 . 174–5 . Jan 1994 . 7514564 . 10.1006/geno.1994.1033 .
• Hashimoto K, Koga M, Motomura T, Kasayama S, Kouhara H, Ohnishi T, Arita N, Hayakawa T, Sato B, Kishimoto T . Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormone-releasing hormone receptor in human pituitary adenomas . The Journal of Clinical Endocrinology and Metabolism . 80 . 10 . 2933–9 . Oct 1995 . 10.1210/jcem.80.10.7559877 . 7559877 .
• Tang J, Lagacé G, Castagné J, Collu R . Identification of human growth hormone-releasing hormone receptor splicing variants . The Journal of Clinical Endocrinology and Metabolism . 80 . 8 . 2381–7 . Aug 1995 . 10.1210/jcem.80.8.7629234 . 7629234 .
• Gaylinn BD, Harrison JK, Zysk JR, Lyons CE, Lynch KR, Thorner MO . Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone . Molecular Endocrinology . 7 . 1 . 77–84 . Jan 1993 . 10.1210/mend.7.1.7680413 . 7680413 . free .
• Gaylinn BD, von Kap-Herr C, Golden WL, Thorner MO . Assignment of the human growth hormone-releasing hormone receptor gene (GHRHR) to 7p14 by in situ hybridization . Genomics . 19 . 1 . 193–5 . Jan 1994 . 8188233 . 10.1006/geno.1994.1045 .
• Wajnrajch MP, Gertner JM, Harbison MD, Chua SC, Leibel RL . Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse . Nature Genetics . 12 . 1 . 88–90 . Jan 1996 . 8528260 . 10.1038/ng0196-88 . 205341432 .
• Netchine I, Talon P, Dastot F, Vitaux F, Goossens M, Amselem S . Extensive phenotypic analysis of a family with growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene . The Journal of Clinical Endocrinology and Metabolism . 83 . 2 . 432–6 . Feb 1998 . 10.1210/jcem.83.2.4528 . 9467553 . free .
• Petersenn S, Rasch AC, Heyens M, Schulte HM . Structure and regulation of the human growth hormone-releasing hormone receptor gene . Molecular Endocrinology . 12 . 2 . 233–47 . Feb 1998 . 9482665 . 10.1210/mend.12.2.0057 . free .
• Maheshwari HG, Silverman BL, Dupuis J, Baumann G . Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh . The Journal of Clinical Endocrinology and Metabolism . 83 . 11 . 4065–74 . Nov 1998 . 10.1210/jcem.83.11.5226 . 9814493 . free .
• Salvatori R, Hayashida CY, Aguiar-Oliveira MH, Phillips JA, Souza AH, Gondo RG, Toledo SP, Conceicão MM, Prince M, Maheshwari HG, Baumann G, Levine MA . Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene . The Journal of Clinical Endocrinology and Metabolism . 84 . 3 . 917–23 . Mar 1999 . 10.1210/jcem.84.3.5599 . 10084571 . 668356 . free .
• Morel G, Gallego R, Boulanger L, Pintos E, Garcia-Caballero T, Gaudreau P . Restricted presence of the growth hormone-releasing hormone receptor to somatotropes in rat and human pituitaries . Neuroendocrinology . 70 . 2 . 128–36 . Aug 1999 . 10461027 . 10.1159/000054467 . 36622953 .
• Rekasi Z, Czompoly T, Schally AV, Halmos G . Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers . Proceedings of the National Academy of Sciences of the United States of America . 97 . 19 . 10561–6 . Sep 2000 . 10962031 . 27064 . 10.1073/pnas.180313297 . 2000PNAS...9710561R . free .
• Salvatori R, Fan X, Phillips JA, Espigares-Martin R, Martin De Lara I, Freeman KL, Plotnick L, Al-Ashwal A, Levine MA . Three new mutations in the gene for the growth hormone (gh)-releasing hormone receptor in familial isolated gh deficiency type ib . The Journal of Clinical Endocrinology and Metabolism . 86 . 1 . 273–9 . Jan 2001 . 10.1210/jcem.86.1.7156 . 11232012 . free .
• Kiaris H, Schally AV, Busto R, Halmos G, Artavanis-Tsakonas S, Varga JL . Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs . Proceedings of the National Academy of Sciences of the United States of America . 99 . 1 . 196–200 . Jan 2002 . 11773624 . 117538 . 10.1073/pnas.012590999 . 2002PNAS...99..196K . free .
• Salvatori R, Fan X, Mullis PE, Haile A, Levine MA . Decreased expression of the GHRH receptor gene due to a mutation in a Pit-1 binding site . Molecular Endocrinology . 16 . 3 . 450–8 . Mar 2002 . 11875102 . 10.1210/mend.16.3.0785 . free .
• Plonowski A, Schally AV, Busto R, Krupa M, Varga JL, Halmos G . Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers . Peptides . 23 . 6 . 1127–33 . Jun 2002 . 12126741 . 10.1016/S0196-9781(02)00043-8 . 39613007 .

External links

• IUPHAR GPCR Database – GHRH receptor

Notes and References

1. Gaylinn BD . Growth hormone releasing hormone receptor . Receptors & Channels . 8 . 3–4 . 155–62 . 2002 . 12529933 . 10.1080/10606820213679 .
2. Web site: Entrez Gene: GHRHR growth hormone releasing hormone receptor.
3. Kovács M, Schally AV, Zarándi M, Groot K . Inhibition of GH release of rats by new potent antagonists of growth hormone-releasing hormone (GH-RH) . Peptides . 18 . 3 . 431–8 . 1997 . 9145432 . 10.1016/S0196-9781(96)00334-8 . 24368945 .
4. Banks WA, Morley JE, Farr SA, Price TO, Ercal N, Vidaurre I, Schally AV . Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice . Proceedings of the National Academy of Sciences of the United States of America . 107 . 51 . 22272–7 . Dec 2010 . 21135231 . 3009756 . 10.1073/pnas.1016369107 . 2010PNAS..10722272B . free .