Growth hormone secretagogue receptor

Growth hormone secretagogue receptor
Identifiers
Symbols GHSR;
External IDs OMIM: 601898 MGI: 2441906 HomoloGene: 57161 IUPHAR: ghrelin GeneCards: GHSR Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2693 208188
Ensembl ENSG00000121853 ENSMUSG00000051136
UniProt Q92847 Q0VBE5
RefSeq (mRNA) NM_004122.2 NM_177330.4
RefSeq (protein) NP_004113.1 NP_796304.1
Location (UCSC) Chr 3:
172.16 – 172.17 Mb		 Chr 3:
27.27 – 27.28 Mb
PubMed search [1] [2]

Growth hormone secretagogue receptor is a G protein-coupled receptor that binds ghrelin[1] and plays a role in energy homeostasis and regulation of body weight.[2]

Contents

Function

Ghrelin is an appetite-regulating factor secreted from peripheral organs that is involved in regulation of energy homoeostasis via binding to the receptor resulting in the secretion of growth hormone by the pituitary gland. [3] The pathway activated by binding of Ghrelin to the Growth hormone secretagogue receptor, GHSR1a, regulates the activation of the downstream mitogen-activated protein kinase, Akt, nitric oxide synthase, and AMPK cascades in different cellular systems.[2] One of the important features of GHSR1a displays constitutive activity possessing basal activity in the absence of an agonist, resulting in a high degree of receptor internalization as well as of signaling activity.[2] Inverse agonists for the ghrelin receptor could be particularly interesting for the treatment of obesity.[4] This activity seems to provide a tonic signal required for the development of normal height, probably through an effect on the GH axis.[5]

Transcripts

Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a.[6]

Selective ligands

A range of selective ligands for the GHSR receptor are now available and are being developed for several clinical applications. GHSR agonists have appetite-stimulating and growth hormone-releasing effects, and are likely to be useful for the treatment of muscle wasting and frailty associated with old-age and degenerative diseases. On the other hand, GHSR antagonists have anorectic effects and are likely to be useful for the treatment of obesity.

Agonists

Antagonists

References

  1. ^ Davenport AP, Bonner TI, Foord SM, Harmar AJ, Neubig RR, Pin JP, Spedding M, Kojima M, Kangawa K (2005). "International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function". Pharmacol. Rev. 57 (4): 541–6. doi:10.1124/pr.57.4.1. PMID 16382107. 
  2. ^ a b c Pazos Y, Casanueva FF, Camiña JP (2007). "Basic aspects of ghrelin action". Vitam. Horm. 77: 89–119. doi:10.1016/S0083-6729(06)77005-4. PMID 17983854. 
  3. ^ Wren AM, Small CJ, Ward HL, et al. (November 2000). "The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion". Endocrinology 141 (11): 4325–8. doi:10.1210/en.141.11.4325. PMID 11089570. http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=11089570. 
  4. ^ Holst B, Cygankiewicz A, Jensen TH, Ankersen M, Schwartz TW (2003). "High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist". Mol. Endocrinol. 17 (11): 2201–10. doi:10.1210/me.2003-0069. PMID 12907757. 
  5. ^ Pantel J, Legendre M, Cabrol S, Hilal L, Hajaji Y, Morisset S, Nivot S, Vie-Luton MP, Grouselle D, de Kerdanet M, Kadiri A, Epelbaum J, Le Bouc Y, Amselem S (2006). "Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature". J Clin Invest. 116 (3): 760–8. doi:10.1172/JCI25303. PMC 1386106. PMID 16511605. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1386106. 
  6. ^ "Entrez Gene: GHSR growth hormone secretagogue receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2693. 

Further reading

External links

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