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Growth hormone secretagogue receptor

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Template:PBB Growth hormone secretagogue receptor (GHSR), 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

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

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

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 (Dec 2005). "International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function". Pharmacological Reviews. 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". Vitamins and Hormones. 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 (ed.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 265–266. ISBN 9780071481274.{{cite book}}: CS1 maint: multiple names: authors list (link)
  4. ^ Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR (Nov 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 (Nov 2003). "High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist". Molecular Endocrinology. 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 (Mar 2006). "Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature". The Journal of Clinical Investigation. 116 (3): 760–8. doi:10.1172/JCI25303. PMC 1386106. PMID 16511605.
  7. ^ "Entrez Gene: GHSR growth hormone secretagogue receptor".
  8. ^ Kordon, Claude; Robinson, I.; Hanoune, Jacques; Dantzer, R. (6 December 2012). Brain Somatic Cross-Talk and the Central Control of Metabolism. Springer Science & Business Media. pp. 42–. ISBN 978-3-642-18999-9. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

Further reading

known previously to be supplied courtesy of Dr. Luc Ver Donck and Dr. Dieder MoecharsPortelli, Jeanelle; Thielemans, Leen; Ver Donck, Luc; Loyens, Ellen; Coppens, Jessica; Aourz, Najat; Aerssens, Jeroen; Vermoesen, Katia; Clinckers, Ralph (2012-07-01). \"Inactivation of the Constitutively Active Ghrelin Receptor Attenuates Limbic Seizure Activity in Rodents\". Neurotherapeutics 9 (3): 658–672. doi:10.1007/s13311-012-0125-x. ISSN 1933-7213. PMC 3441926. PMID 22669710. "},"attrs":{}}">[1]

  • Smith RG, Leonard R, Bailey AR, Palyha O, Feighner S, Tan C, Mckee KK, Pong SS, Griffin P, Howard A (Feb 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 (Dec 2002). "Structure and regulation of the growth hormone secretagogue receptor". Minerva Endocrinologica. 27 (4): 243–56. PMID 12511847.
  • Holst B, Schwartz TW (Mar 2006). "Ghrelin receptor mutations--too little height and too much hunger". The Journal of Clinical Investigation. 116 (3): 637–41. doi:10.1172/JCI27999. PMC 1386123. PMID 16511600.
  • Nogueiras R, Perez-Tilve D, Wortley KE, Tschöp M (Jun 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 (Jan 1977). "[Giardia lamblia and other intestinal parasites in children in day-institutions. Incidence and significance]". Ugeskrift for Laeger. 140 (1): 14–7. PMID 601898.
  • Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH (Aug 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, Hreniuk DL, Tan CP, Phillips MS, Smith RG, Van der Ploeg LH, Howard AD (Apr 1997). "Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors". Molecular Endocrinology. 11 (4): 415–23. doi:10.1210/me.11.4.415. PMID 9092793.
  • Kaji H, Tai S, Okimura Y, Iguchi G, Takahashi Y, Abe H, Chihara K (Dec 1998). "Cloning and characterization of the 5'-flanking region of the human growth hormone secretagogue receptor gene". The Journal of Biological Chemistry. 273 (51): 33885–8. doi:10.1074/jbc.273.51.33885. PMID 9852035.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  • Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (Dec 1999). "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 (Jan 2001). "Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland". Journal of Endocrinological Investigation. 24 (1): RC1-3. doi:10.1007/bf03343800. PMID 11227737.
  • Tannenbaum GS, Bowers CY (Feb 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, Beil FU, Schulte HM (Jun 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, Kuriyama H, Ohata H, Tamura H, Kamegai J, Sugihara H, Oikawa S, Wakabayashi I (Jun 2002). "Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity". The Journal of Clinical Investigation. 109 (11): 1429–36. doi:10.1172/JCI13300. PMC 150991. PMID 12045256.
  • Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (Dec 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Gaytan F, Barreiro ML, Chopin LK, Herington AC, Morales C, Pinilla L, Casanueva FF, Aguilar E, Diéguez C, Tena-Sempere M (Feb 2003). "Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary". The Journal of Clinical Endocrinology and Metabolism. 88 (2): 879–87. doi:10.1210/jc.2002-021196. PMID 12574228.
  • Dass NB, Munonyara M, Bassil AK, Hervieu GJ, Osbourne S, Corcoran S, Morgan M, Sanger GJ (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, Magoulas C, Sesay A, Houston P, Mathers K, Robinson I (Apr 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, Schäuble N, Friedel S, Lichtner P, Fontenla-Horro F, Wudy S, Hagemann S, Gortner L, Huse K, Remschmidt H, Bettecken T, Meitinger T, Schäfer H, Hebebrand J, Hinney A (Jan 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". The Journal of Clinical Endocrinology and Metabolism. 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.

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