Growth-hormone-releasing hormone receptor

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.^[5] 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.

GHRHR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2XDG
Identifiers
Aliases	GHRHR, GHRFR, GRFR, IGHD1B, growth hormone releasing hormone receptor, IGHD4
External IDs	OMIM: 139191; MGI: 95710; HomoloGene: 640; GeneCards: GHRHR; OMA:GHRHR - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p14.3 Start 30,938,669 bp[1] End 30,993,254 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 B3|6 27.38 cM Start 55,353,280 bp[2] End 55,365,515 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pituitary gland anterior pituitary oocyte secondary oocyte hypothalamus cingulate gyrus anterior cingulate cortex amygdala Descending thoracic aorta nucleus accumbens Top expressed in pituitary gland anterior pituitary choroid plexus of fourth ventricle entorhinal cortex CA3 field soleus muscle proximal tubule right kidney yolk sac tibialis anterior muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity growth factor binding signal transducer activity peptide hormone binding protein binding growth hormone-releasing hormone receptor activity transmembrane signaling receptor activity G protein-coupled peptide receptor activity Cellular component cytoplasm integral component of membrane membrane nuclear matrix plasma membrane secretory granule cell surface nuclear inner membrane sarcolemma nuclear outer membrane Biological process adenylate cyclase-activating G protein-coupled receptor signaling pathway determination of adult lifespan adenylate cyclase-modulating G protein-coupled receptor signaling pathway response to glucocorticoid cell maturation adenohypophysis development water homeostasis activation of adenylate cyclase activity response to estrogen mammary gland development response to insulin positive regulation of circadian sleep/wake cycle, non-REM sleep cell surface receptor signaling pathway regulation of insulin-like growth factor receptor signaling pathway positive regulation of insulin-like growth factor receptor signaling pathway growth hormone secretion positive regulation of growth hormone secretion positive regulation of cell population proliferation positive regulation of multicellular organism growth cellular response to insulin stimulus somatotropin secreting cell development regulation of protein metabolic process lactation regulation of intracellular steroid hormone receptor signaling pathway hormone metabolic process positive regulation of hormone secretion cAMP-mediated signaling cellular response to glucose stimulus signal transduction multicellular organismal reproductive process G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2692 14602 Ensembl ENSG00000106128 ENSMUSG00000004654 UniProt Q02643 P32082 RefSeq (mRNA) NM_000823 NM_001009824 NM_001003685 RefSeq (protein) NP_000814 NP_001003685 Location (UCSC) Chr 7: 30.94 – 30.99 Mb Chr 6: 55.35 – 55.37 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[6]

Ligands

Agonists

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

Antagonists

• MZ-5-156^[7][8]

References

1. GRCh38: Ensembl release 89: ENSG00000106128 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004654 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Gaylinn BD (2002). "Growth hormone releasing hormone receptor". Receptors & Channels. 8 (3–4): 155–62. doi:10.1080/10606820213679. PMID 12529933.
6. "Entrez Gene: GHRHR growth hormone releasing hormone receptor".
7. Kovács M, Schally AV, Zarándi M, Groot K (1997). "Inhibition of GH release of rats by new potent antagonists of growth hormone-releasing hormone (GH-RH)". Peptides. 18 (3): 431–8. doi:10.1016/S0196-9781(96)00334-8. PMID 9145432. S2CID 24368945.
8. Banks WA, Morley JE, Farr SA, Price TO, Ercal N, Vidaurre I, Schally AV (Dec 2010). "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. Bibcode:2010PNAS..10722272B. doi:10.1073/pnas.1016369107. PMC 3009756. PMID 21135231.

Further reading

• Gaylinn BD (Apr 1999). "Molecular and cell biology of the growth hormone-releasing hormone receptor". Growth Hormone & IGF Research. 9 Suppl A: 37–44. doi:10.1016/S1096-6374(99)80008-2. PMID 10429879.
• Lin-Su K, Wajnrajch MP (Dec 2002). "Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor". Reviews in Endocrine & Metabolic Disorders. 3 (4): 313–23. doi:10.1023/A:1020949507265. PMID 12424433. S2CID 6263928.
• Mayo KE (Oct 1992). "Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone". Molecular Endocrinology. 6 (10): 1734–44. doi:10.1210/mend.6.10.1333056. PMID 1333056.
• Squire J, Zhou A, Hassel BA, Nie H, Silverman RH (Jan 1994). "Localization of the interferon-induced, 2-5A-dependent RNase gene (RNS4) to human chromosome 1q25". Genomics. 19 (1): 174–5. doi:10.1006/geno.1994.1033. PMID 7514564.
• Hashimoto K, Koga M, Motomura T, Kasayama S, Kouhara H, Ohnishi T, Arita N, Hayakawa T, Sato B, Kishimoto T (Oct 1995). "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. doi:10.1210/jcem.80.10.7559877. PMID 7559877.
• Tang J, Lagacé G, Castagné J, Collu R (Aug 1995). "Identification of human growth hormone-releasing hormone receptor splicing variants". The Journal of Clinical Endocrinology and Metabolism. 80 (8): 2381–7. doi:10.1210/jcem.80.8.7629234. PMID 7629234.
• Gaylinn BD, Harrison JK, Zysk JR, Lyons CE, Lynch KR, Thorner MO (Jan 1993). "Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone". Molecular Endocrinology. 7 (1): 77–84. doi:10.1210/mend.7.1.7680413. PMID 7680413.
• Gaylinn BD, von Kap-Herr C, Golden WL, Thorner MO (Jan 1994). "Assignment of the human growth hormone-releasing hormone receptor gene (GHRHR) to 7p14 by in situ hybridization". Genomics. 19 (1): 193–5. doi:10.1006/geno.1994.1045. PMID 8188233.
• Wajnrajch MP, Gertner JM, Harbison MD, Chua SC, Leibel RL (Jan 1996). "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. doi:10.1038/ng0196-88. PMID 8528260. S2CID 205341432.
• Netchine I, Talon P, Dastot F, Vitaux F, Goossens M, Amselem S (Feb 1998). "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. doi:10.1210/jcem.83.2.4528. PMID 9467553.
• Petersenn S, Rasch AC, Heyens M, Schulte HM (Feb 1998). "Structure and regulation of the human growth hormone-releasing hormone receptor gene". Molecular Endocrinology. 12 (2): 233–47. doi:10.1210/mend.12.2.0057. PMID 9482665.
• Maheshwari HG, Silverman BL, Dupuis J, Baumann G (Nov 1998). "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. doi:10.1210/jcem.83.11.5226. PMID 9814493.
• 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 (Mar 1999). "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. doi:10.1210/jcem.84.3.5599. PMID 10084571. S2CID 668356.
• Morel G, Gallego R, Boulanger L, Pintos E, Garcia-Caballero T, Gaudreau P (Aug 1999). "Restricted presence of the growth hormone-releasing hormone receptor to somatotropes in rat and human pituitaries". Neuroendocrinology. 70 (2): 128–36. doi:10.1159/000054467. PMID 10461027. S2CID 36622953.
• Rekasi Z, Czompoly T, Schally AV, Halmos G (Sep 2000). "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. Bibcode:2000PNAS...9710561R. doi:10.1073/pnas.180313297. PMC 27064. PMID 10962031.
• Salvatori R, Fan X, Phillips JA, Espigares-Martin R, Martin De Lara I, Freeman KL, Plotnick L, Al-Ashwal A, Levine MA (Jan 2001). "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. doi:10.1210/jcem.86.1.7156. PMID 11232012.
• Kiaris H, Schally AV, Busto R, Halmos G, Artavanis-Tsakonas S, Varga JL (Jan 2002). "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. Bibcode:2002PNAS...99..196K. doi:10.1073/pnas.012590999. PMC 117538. PMID 11773624.
• Salvatori R, Fan X, Mullis PE, Haile A, Levine MA (Mar 2002). "Decreased expression of the GHRH receptor gene due to a mutation in a Pit-1 binding site". Molecular Endocrinology. 16 (3): 450–8. doi:10.1210/mend.16.3.0785. PMID 11875102.
• Plonowski A, Schally AV, Busto R, Krupa M, Varga JL, Halmos G (Jun 2002). "Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers". Peptides. 23 (6): 1127–33. doi:10.1016/S0196-9781(02)00043-8. PMID 12126741. S2CID 39613007.

External links

• IUPHAR GPCR Database – GHRH receptor Archived 2016-03-03 at the Wayback Machine
• somatotropin+releasing+hormone+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.