Physiological Function of Growth Hormone Secretagogue Receptors in the Cardiovascular System

  • H. Ong
  • D. Lamontagne
  • A. Demers
  • S. Marleau
Conference paper


Growth hormone secretagogues (GHS) consist of a series of small enkephalin derived peptides identified as growth hormone-releasing peptides (GHRPs) (Bowers, 1993) and non-peptidyl derivatives modeled from GHRPs (Smith et al., 1997). To this class of compounds is recently added a new member, ghrelin, an endogenous 28 amino acid polypeptide isolated from the stomach (Kojima et al., 1999). GHS share a common activity in stimulating the release of growth hormone (GH) from the pituitary in several animal species and in man (Ghigo et al., 2001). The GH release is mediated through the binding of GHS to a G protein-coupled receptor identified by expression cloning as GHS-Ria or ghrelin receptor, for which mRNA expression as well as protein receptor localization are mainly confined to the hypothalamus and the pituitary (Howard et al., 1996).


Growth Hormone Ischemic Precondition Stroke Volume Index Growth Hormone Secretagogue Growth Hormone Secretagogue Receptor 
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  1. Bedendi I., Gallo M.P., Malan D., Levi R.C. and Alloatti G. (2001). Role of endothelial cells in modulation of contractility induced by hexarelin in rat ventricle. Life Sci, 69, 2189–2201.PubMedCrossRefGoogle Scholar
  2. Berti F., Rossoni G., and De Gennaro Colonna V. (1999). Hexarelin, a synthetic growth hormone secretagogue, exhibits protectant activity in experimental myocardial ischemia and reperfusion. In Growth hormone secretagogues, eds E. Ghigo, M. Boghen, F.F. Casanueva and C. Dieguez, pp. 301–314. New York, Elsevier Science.CrossRefGoogle Scholar
  3. Bisi G., Podio V.,Valetto M.R., Broglio F., Bertuccio G., Del Rio G.,Arvat E., Boghen M.F., Deghenghi R., Muccioli G.,Ong H. and Ghigo E. (1999). Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest, 22, 266–272.Google Scholar
  4. Bodart V., Bouchard J.F., McNicoll N., Escher E., Carriere P., Ghigo E., Sejlitz T., Sirois M.G., Lamontagne D. and Ong, H. (1999). Identification and characterization of a new growth hormone-releasing peptide receptor in the heart. Circ Res, 85, 796–802.PubMedCrossRefGoogle Scholar
  5. Bodart V., Febbraio M., Demers A., McNicoll N., Pohankova P., Perreault A., Sejlitz T., Escher E., Silverstein R.L., Lamontagne D. and Ong, H. (2002). CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res, 90, 844–849PubMedCrossRefGoogle Scholar
  6. Bouchard J.F. and Lamontagne D. (1996). Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury. Am J Physiol, 271, H1801–H186.PubMedGoogle Scholar
  7. Bowers C.Y. (1993). GH-releasing peptides-structure and kinetics. J Pediatr Endocrinol, 6, 21–31.PubMedCrossRefGoogle Scholar
  8. Cassoni P., Papotti M., Ghè C., Catapano F., Sapino A., Graziani A., Deghenghi R., Reissmann T., Ghigo E. and Muccioli G. (2001). Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab, 86, 1738–1745.PubMedCrossRefGoogle Scholar
  9. Date Y., Nakazato M., Hashiguchi S., Dezaki K., Mondal M.S., Hosoda H., Kojima M., Kangawa K.,Arima T., Matsuo H., Yada T.and Matsukura S. (2002). Ghrelin is present in pancreatic a-cells of humans and rats and stimulates insulin secretion. Diabetes, 51, 124–129.Google Scholar
  10. De Gennaro Colonna V., Rossoni G., Bernareggi M., Muller E.E. and Berti F. (1997). Cardiac ischemia and impairment of vascular endothelium function in hearts from growth hormone-deficient rats: protection by hexarelin. Eur J Pharmacol, 334, 201–207.PubMedCrossRefGoogle Scholar
  11. De Gennaro Colonna V., Rossoni G., Cocchi D., Rigamonti A.E., Berti F.and Muller E.E. (2000). Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats. J Endocrinol, 166, 529–536.PubMedCrossRefGoogle Scholar
  12. Febbraio M., Hajjar D.P., and Silverstein R.L. (2001). CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest, 108, 785–791.PubMedGoogle Scholar
  13. Filigheddu N., Fubini A., Baldanzi G., Cutrupi S., Ghe C., Catapano F., Broglio F., Bosia A., Papotti M., Muccioli G., Ghigo E., Deghenghi R. and Graziani A. (2001). Hexarelin protects H9c2 cardiomyocytes from doxorubicin-induced cell death. Endocrine, 14, 113–119PubMedCrossRefGoogle Scholar
  14. Ghigo E., Arvat E., Giordano R., Broglio F.,Gianotti L., Maccario M., Bisi G., Graziani A., Papotti M., Muccioli G., Deghenghi R. and Camanni F. (2001). Biologic activ ities of growth hormone secretagogues in humans. Endocrine, 14, 87–93.Google Scholar
  15. Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B., and Korbonits M. (2002). The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab, 87, 2988.PubMedCrossRefGoogle Scholar
  16. Hattori N., Saito T., Yagyu T., Jiang B.-H., Kitagawa K., and Inagaki C. (2001). GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab, 86, 4284–4291.PubMedCrossRefGoogle Scholar
  17. Howard A.D., Feighner S., Cully D.F., Arena J.P., Liberator P.A., Resenblum C.I., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C, Chou M., Liu K.K., McKee K.K., Pong S.S., Chaung L.Y., Elbrecht A., Dashkevicz M., Heavens R., Rigby M., Sirinathsinghji D.J., Dean D.C., Mellilo D.G. and Van der Ploeg L.H. (1996). A receptor in pituitary and hypothalamus that functions in growth hormone release. Science, 273, 974–977PubMedCrossRefGoogle Scholar
  18. Katugampola S.D., Pallikaros Z. and Davenport M. (2001). 125I-His(9)-ghrelin, a novel radiologand for localizing GHS orphan receptors in human and rat tissue: up-regula-tion of receptors with atherosclerosis. Br J Pharmacol, 134, 143–149.PubMedCrossRefGoogle Scholar
  19. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H. and Kangawa K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402, 656–660.PubMedCrossRefGoogle Scholar
  20. Locatelli V., Rossoni G., Schweiger R, Torsello A., De Gennaro C.V., Bernareggi M., Deghenghi R., Muller E.E. and Berti F. (1999). Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology, 140, 4024–4031.PubMedCrossRefGoogle Scholar
  21. MacAndrew J.T., Ellery S.S., Parry M.A., Pan L.C. and Black S.C. (2001). Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury. Eur J Pharmacol, 432, 195–202.PubMedCrossRefGoogle Scholar
  22. Muccioli G., Broglio F., Valetto M.R., Ghè C, Catapano F., Graziani A., Papotti M., Bisi G., Deghenghi R. and Ghigo E. (2000). Growth hormone-releasing peptides and the cardiovascular system. Ann Endocrinol, 61, 27–31.Google Scholar
  23. Musters R.J., van der Meulen E.T., Zuidwijk M., Muller A., Simonides W.S., Banerjee A. and van Hardeveld C. (1999). PKC-dependent preconditionning with norepinephrine protects sarcoplasmic reticulum function in rat trabeculae following metabolic inhibition. J Mol Cell Cardiol, 31, 1083–1094.CrossRefGoogle Scholar
  24. Nagaya N., Kojima M., Uematsu M., Yamagishi M., Hosoda H., Oya H., Hayashi Y. and Kangawa K. (2001). Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regulatory Integrative Comp Physiol, 280, R1483–R1487.Google Scholar
  25. Okumura H., Nagaya N., Enomoto M., Nakagawa E., Oya H. and Kangawa K. (2002). Vasodilatory effect of ghrelin and endogenous peptides from the stomach. J Cardiovasc Pharmacol, 39, 779–783.PubMedCrossRefGoogle Scholar
  26. Ong H., Bodart V, McNicoll N., Lamontagne D. and Bouchard J.E (1998a). Binding sites for growth hormone-releasing peptide. Growth Horm IGF Res, 8 (Suppl B), 137–140.CrossRefGoogle Scholar
  27. Ong H, McNicoll N., Escher E., Collu R., Deghenghi R., Locatelli V, Ghigo E., Muccioli G., Boghen M. and Nilsson A. (1998b). Identification of a pituitary growth hormone-releasing peptide (GHRP) receptor subtype by photoaffmity labeling. Endocrinology, 139, 432–435.CrossRefGoogle Scholar
  28. Papotti M., Ghè C, Cassoni P., Catapano F., Deghenghi R., Ghigo E. and Muccioli G. (2000). Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab, 85, 3803–3807.PubMedCrossRefGoogle Scholar
  29. Rossoni G., De Gennaro Colonna V., Bernareggi M., Polvani G.L., Muller E.E. and Berti F. (1998). Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats. J Cardiovasc Phamacol, 32, 260–265.CrossRefGoogle Scholar
  30. Smith R.G., Van der Ploeg L.H.T., Howard A.D., Feighner S.D., Cheng K., Hickey G.J., Wyvratt M.J. Jr, Fisher M.H., Nargund R.P. and Patchett A.A. (1997). Peptidomimetic regulation of growth hormone secretion. Endoc Rev, 18, 621–645.CrossRefGoogle Scholar
  31. Tivesten Å., Bollano E., Caidahl K., Kujacic V, Sun X.Y., Hedner T., Hjalmarson Å., Bengtsson B.-Å. and Isgaard J. (2000). The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology, 141, 60–66.PubMedCrossRefGoogle Scholar
  32. Tschöp M., Smiley D.L. and Heiman M.L. (2000). Ghrelin induces adiposity in rodents. Nature, 407,908–913.PubMedCrossRefGoogle Scholar
  33. Weekers R, Van Herck E., Isgaard J. and Van den Berghe G. (2000). Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model. Endocrinology, 141, 3993–3999.PubMedCrossRefGoogle Scholar
  34. Wiley K.E. and Davenport A.P. (2002). Comparison of vasodilators in human mammary arteries: ghrelin is a potent physiological antagonist of endothelin. Br J Pharmacol, 136, 1146–1152.PubMedCrossRefGoogle Scholar
  35. Wren A.A., Small C.J., Abbott CR., Dhillo W.S., Seal L.J., Cohen M.A., Batterham R.L., Taheri S., Stanley S.A., Ghatei M.A. and Bloom S.R. (2001). Ghrelin causes hyperpha-gia and obesity in rats. Diabetes, 50, 2540–2547.PubMedCrossRefGoogle Scholar
  36. Wu D., Clarke I.J. and Chen C. (1997). The role of protein kinase C (PKC) in growth hormone (GH) secretion induced by GH-releasing factor (GRF) and GH-releasing peptides (GHRP) in cultured ovine somatotrophs. J Endocrinol, 154, 219–230.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2003

Authors and Affiliations

  • H. Ong
  • D. Lamontagne
  • A. Demers
  • S. Marleau

There are no affiliations available

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