Growth hormone secretagogue receptor

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Growth hormone secretagogue receptor
Identifiers
Symbol GHSR
External IDs OMIM601898 MGI2441906 HomoloGene57161 IUPHAR: ghrelin receptor ChEMBL: 4616 GeneCards: GHSR Gene
RNA expression pattern
PBB GE GHSR 221360 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2693 208188
Ensembl ENSG00000121853 ENSMUSG00000051136
UniProt Q92847 Q99P50
RefSeq (mRNA) NM_004122 NM_177330
RefSeq (protein) NP_004113 NP_796304
Location (UCSC) Chr 3:
172.16 – 172.17 Mb
Chr 3:
27.37 – 27.38 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]

Function[edit]

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[edit]

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[edit]

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[edit]

Antagonists[edit]

References[edit]

  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/endo.141.11.7873. 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. 
  6. ^ "Entrez Gene: GHSR growth hormone secretagogue receptor". 

Further reading[edit]

External links[edit]

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