Growth hormone secretagogue receptor

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Growth hormone secretagogue receptor
Identifiers
SymbolsGHSR;
External IDsOMIM: 601898 MGI: 2441906 HomoloGene: 57161 IUPHAR: ghrelin GeneCards: GHSR Gene
RNA expression pattern
250px
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez2693208188
EnsemblENSG00000121853ENSMUSG00000051136
UniProtQ92847Q0VBE5
RefSeq (mRNA)NM_004122NM_177330
RefSeq (protein)NP_004113NP_796304
Location (UCSC)Chr 3:
173.65 - 173.65 Mb		Chr 3:
27.56 - 27.57 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

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

  • A-778,193

References

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Further reading

  • Smith RG, Leonard R, Bailey AR; et al. (2001). "Growth hormone secretagogue receptor family members and ligands". Endocrine. 14 (1): 9–14. doi:10.1385/ENDO:14:1:009. PMID 11322507. 
  • Petersenn S (2003). "Structure and regulation of the growth hormone secretagogue receptor". Minerva Endocrinol. 27 (4): 243–56. PMID 12511847. 
  • Holst B, Schwartz TW (2006). "Ghrelin receptor mutations--too little height and too much hunger". J. Clin. Invest. 116 (3): 637–41. doi:10.1172/JCI27999. PMC 1386123 Freely accessible. PMID 16511600. 
  • Nogueiras R, Perez-Tilve D, Wortley KE, Tschöp M (2006). "Growth hormone secretagogue (ghrelin-) receptors--a complex drug target for the regulation of body weight". CNS & neurological disorders drug targets. 5 (3): 335–43. doi:10.2174/187152706777452227. PMID 16787234. 
  • Engbaek K (1978). "[Giardia lamblia and other intestinal parasites in children in day-institutions. Incidence and significance]". Ugeskr. Laeg. 140 (1): 14–7. PMID 601898. 
  • Howard AD, Feighner SD, Cully DF; et al. (1996). "A receptor in pituitary and hypothalamus that functions in growth hormone release". Science. 273 (5277): 974–7. doi:10.1126/science.273.5277.974. PMID 8688086. 
  • McKee KK, Palyha OC, Feighner SD; et al. (1997). "Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors". Mol. Endocrinol. 11 (4): 415–23. doi:10.1210/me.11.4.415. PMID 9092793. 
  • Kaji H, Tai S, Okimura Y; et al. (1999). "Cloning and characterization of the 5'-flanking region of the human growth hormone secretagogue receptor gene". J. Biol. Chem. 273 (51): 33885–8. doi:10.1074/jbc.273.51.33885. PMID 9852035. 
  • Kojima M, Hosoda H, Date Y; et al. (2000). "Ghrelin is a growth-hormone-releasing acylated peptide from stomach". Nature. 402 (6762): 656–60. doi:10.1038/45230. PMID 10604470. 
  • Deghenghi R, Papotti M, Ghigo E, Muccioli G (2001). "Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland". J. Endocrinol. Invest. 24 (1): RC1–3. PMID 11227737. 
  • Tannenbaum GS, Bowers CY (2001). "Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin". Endocrine. 14 (1): 21–7. doi:10.1385/ENDO:14:1:021. PMID 11322498. 
  • Petersenn S, Rasch AC, Penshorn M; et al. (2001). "Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor". Endocrinology. 142 (6): 2649–59. doi:10.1210/en.142.6.2649. PMID 11356716. 
  • Shuto Y, Shibasaki T, Otagiri A; et al. (2002). "Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity". J. Clin. Invest. 109 (11): 1429–36. doi:10.1172/JCI13300. PMC 150991 Freely accessible. PMID 12045256. 
  • Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241 Freely accessible. PMID 12477932. 
  • Gaytan F, Barreiro ML, Chopin LK; et al. (2003). "Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary". J. Clin. Endocrinol. Metab. 88 (2): 879–87. doi:10.1210/jc.2002-021196. PMID 12574228. 
  • Dass NB, Munonyara M, Bassil AK; et al. (2003). "Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin". Neuroscience. 120 (2): 443–53. doi:10.1016/S0306-4522(03)00327-0. PMID 12890514. 
  • Lall S, Balthasar N, Carmignac D; et al. (2004). "Physiological studies of transgenic mice overexpressing growth hormone (GH) secretagogue receptor 1A in GH-releasing hormone neurons". Endocrinology. 145 (4): 1602–11. doi:10.1210/en.2003-1509. PMID 14701677. 
  • Wang HJ, Geller F, Dempfle A; et al. (2004). "Ghrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature". J. Clin. Endocrinol. Metab. 89 (1): 157–62. doi:10.1210/jc.2003-031395. PMID 14715843. 

External links

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

Class A: Rhodopsin like
α1 (A, B, D) · α2 (A, B, C) · β1 · β2 · β3
Adenosine (A1, A2A, A2B, A3) · P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(all but 5-HT3) 5-HT1 (A, B, D, E, F) · 5-HT2 (A, B, C) · 5-HT (4, 5A, 6, 7)
Other
Acetylcholine (M1, M2, M3, M4, M5) · Dopamine (D1, D2, D3, D4, D5) · Histamine (H1, H2, H3, H4) · Melatonin (1A, 1B, 1C) · TAAR (1, 2, 3, 5, 6, 8, 9)
Metabolites and
signaling molecules
CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other
Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate
Peptide
B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other
Miscellaneous
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other
Class B: Secretin like
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other
Class C: Metabotropic
glutamate / pheromone
TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other
Class F:
Frizzled / Smoothened
Frizzled
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened


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  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. ↑ 2.0 2.1 2.2 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. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  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 Freely accessible. PMID 16511605. 
  6. ↑ "Entrez Gene: GHSR growth hormone secretagogue receptor". 
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