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, or ghrelin receptor, is a G protein-coupled receptor that binds ghrelin[1] and plays a role in energy homeostasis and regulation of body weight.[2] In the brain, they are located in the hypothalamic ventromedial nucleus and arcuate nucleus, as well as in ventral tegmental area dopamine neurons projecting to the nucleus accumbens.[3]

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. [4] 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.[5] This activity seems to provide a tonic signal required for the development of normal height, probably through an effect on the GH axis.[6]

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.[7]

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. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10:Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 265–266. ISBN 9780071481274. The best described site of action of ghrelin is the VMH and arcuate nucleus, but ghrelin receptors are also expressed in the brain’s reward pathways (eg, VTA dopamine neurons) and may stimulate feeding through this action as well. ... It is very interesting then, as mentioned above, that orexin, leptin, and ghrelin receptors are expressed in the VTA, and MC4 and MCH receptors are enriched in the nucleus accumbens. There is increasing evidence that some of the actions of these feeding peptides are mediated at the level of the VTA-NAc circuit: recent studies, for example, have shown that injection of leptin into the VTA suppresses feeding behavior, while RNAi (RNA interference; Chapter 4) mediated-knockdown of leptin receptors in the VTA increases food intake, sensitivity to highly palatable foods, and locomotor activity. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ "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.