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Gene Review

GHRL  -  ghrelin/obestatin prepropeptide

Homo sapiens

Synonyms: Appetite-regulating hormone, Growth hormone secretagogue, Growth hormone-releasing peptide, MTLRP, Motilin-related peptide, ...
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Disease relevance of GHRL


Psychiatry related information on GHRL


High impact information on GHRL


Chemical compound and disease context of GHRL

  • On the other hand, in obesity ghrelin shows preserved influence on PRL, ACTH, and insulin secretion as well as in glucose levels [15].
  • Similar to what has been reported for ghrelin administration, our subjects ate 35.9 +/- 10.9% more when infused with GHRP-2 vs. saline, with every subject increasing their intake even when calculated per kg body weight (136.0 +/- 13.0 kJ/kg [32.5 +/- 3.1 kcal/kg] vs. 101.3 +/- 10.5 kJ/kg [24.2 +/- 2.5 kcal/kg], p = 0.008) [16].
  • Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans [10].
  • Using pertussis toxin and the phospholipase C inhibitor U-73122, we show that ghrelin signals through the Gq pathway in the RC-4B/C.40 cells [17].
  • While oestrogen, progesterone and growth factors, including growth hormone (GH), are clearly implicated in the pathogenesis of breast cancer, there is now evidence that the newly described ghrelin axis is also involved [18].

Biological context of GHRL


Anatomical context of GHRL


Associations of GHRL with chemical compounds


Physical interactions of GHRL


Regulatory relationships of GHRL

  • In conclusion, our results demonstrate that the ovarian surface epithelium and related tumors are potential targets for systemic or locally produced ghrelin because they express the functional type 1a GHS-R [32].
  • In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man [33].
  • Both SRIF and CST similarly inhibited (p < 0.01) circulating ghrelin levels of about 55% [34].
  • Ghrelin is an orexigenic hormone that induces NPY release and inhibits proinflammatory cytokines via its antagonistic relationship with leptin [2].
  • In conclusion, ghrelin-induced GH secretion was severely blunted in patients with active Cushing's syndrome, in addition to a remarkable hyper-response in ACTH and cortisol secretion [35].

Other interactions of GHRL

  • We studied five lean and five obese young men [ages: 24.2 +/- 1.0 (lean) and 21.8 +/- 1.6 (obese) years (difference not significant); body mass indexes: 35.0 +/- 1.3 and 23.0 +/- 0.3 kg/m2 (P = 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points [20].
  • Together, these findings suggest a novel role for the ghrelin/GHS-R axis in astrocytoma cell migration and invasiveness of cancers of central nervous system origin [5].
  • Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase [21].
  • PYY, ghrelin, GIP, insulin, and glucose concentrations and four markers of satiety were measured for 240 min after a mixed meal [9].
  • To clarify the mechanisms of action underlying the GH-releasing activity of ghrelin in humans, its interaction with GHRH and HEX was also studied [25].
  • An additive effect of high leptin and low ghrelin on metabolic disturbances was observed: low ghrelin concentration (adjusted for age and sex) (P < 0.001) was associated with the MS and type 2 diabetes in the highest but not in the lower leptin quartiles [36].

Analytical, diagnostic and therapeutic context of GHRL



  1. Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students. Hinney, A., Hoch, A., Geller, F., Schäfer, H., Siegfried, W., Goldschmidt, H., Remschmidt, H., Hebebrand, J. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  2. Polymorphisms in ghrelin and neuropeptide Y genes are associated with non-Hodgkin lymphoma. Skibola, D.R., Smith, M.T., Bracci, P.M., Hubbard, A.E., Agana, L., Chi, S., Holly, E.A. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  3. The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Jeffery, P.L., Herington, A.C., Chopin, L.K. Cytokine Growth Factor Rev. (2003) [Pubmed]
  4. Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth. Volante, M., Allia, E., Fulcheri, E., Cassoni, P., Ghigo, E., Muccioli, G., Papotti, M. Am. J. Pathol. (2003) [Pubmed]
  5. Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility. Dixit, V.D., Weeraratna, A.T., Yang, H., Bertak, D., Cooper-Jenkins, A., Riggins, G.J., Eberhart, C.G., Taub, D.D. J. Biol. Chem. (2006) [Pubmed]
  6. Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. Barazzoni, R., Zanetti, M., Ferreira, C., Vinci, P., Pirulli, A., Mucci, M., Dore, F., Fonda, M., Ciocchi, B., Cattin, L., Guarnieri, G. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  7. Serum ghrelin as a marker of atrophic body gastritis in patients with parietal cell antibodies. Checchi, S., Montanaro, A., Pasqui, L., Ciuoli, C., Cevenini, G., Sestini, F., Fioravanti, C., Pacini, F. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  8. Variants in the ghrelin gene are associated with metabolic syndrome in the Old Order Amish. Steinle, N.I., Pollin, T.I., O'Connell, J.R., Mitchell, B.D., Shuldiner, A.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  9. Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents. Stock, S., Leichner, P., Wong, A.C., Ghatei, M.A., Kieffer, T.J., Bloom, S.R., Chanoine, J.P. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  10. Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans. Schüssler, P., Uhr, M., Ising, M., Weikel, J.C., Schmid, D.A., Held, K., Mathias, S., Steiger, A. Psychoneuroendocrinology (2006) [Pubmed]
  11. Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Dzaja, A., Dalal, M.A., Himmerich, H., Uhr, M., Pollmächer, T., Schuld, A. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  12. Ghrelin: structure and function. Kojima, M., Kangawa, K. Physiol. Rev. (2005) [Pubmed]
  13. Elevated plasma ghrelin levels in Prader Willi syndrome. Cummings, D.E., Clement, K., Purnell, J.Q., Vaisse, C., Foster, K.E., Frayo, R.S., Schwartz, M.W., Basdevant, A., Weigle, D.S. Nat. Med. (2002) [Pubmed]
  14. A role for ghrelin in the central regulation of feeding. Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., Matsukura, S. Nature (2001) [Pubmed]
  15. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity. Tassone, F., Broglio, F., Destefanis, S., Rovere, S., Benso, A., Gottero, C., Prodam, F., Rossetto, R., Gauna, C., van der Lely, A.J., Ghigo, E., Maccario, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  16. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. Laferrère, B., Abraham, C., Russell, C.D., Bowers, C.Y. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  17. Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C. Falls, H.D., Dayton, B.D., Fry, D.G., Ogiela, C.A., Schaefer, V.G., Brodjian, S., Reilly, R.M., Collins, C.A., Kaszubska, W. J. Mol. Endocrinol. (2006) [Pubmed]
  18. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Jeffery, P.L., Murray, R.E., Yeh, A.H., McNamara, J.F., Duncan, R.P., Francis, G.D., Herington, A.C., Chopin, L.K. Endocr. Relat. Cancer (2005) [Pubmed]
  19. International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Davenport, A.P., Bonner, T.I., Foord, S.M., Harmar, A.J., Neubig, R.R., Pin, J.P., Spedding, M., Kojima, M., Kangawa, K. Pharmacol. Rev. (2005) [Pubmed]
  20. Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Yildiz, B.O., Suchard, M.A., Wong, M.L., McCann, S.M., Licinio, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  21. Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase. Beaumont, N.J., Skinner, V.O., Tan, T.M., Ramesh, B.S., Byrne, D.J., MacColl, G.S., Keen, J.N., Bouloux, P.M., Mikhailidis, D.P., Bruckdorfer, K.R., Vanderpump, M.P., Srai, K.S. J. Biol. Chem. (2003) [Pubmed]
  22. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. Gnanapavan, S., Kola, B., Bustin, S.A., Morris, D.G., McGee, P., Fairclough, P., Bhattacharya, S., Carpenter, R., Grossman, A.B., Korbonits, M. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  23. High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist. Holst, B., Cygankiewicz, A., Jensen, T.H., Ankersen, M., Schwartz, T.W. Mol. Endocrinol. (2003) [Pubmed]
  24. Effects of modified sham feeding on ghrelin levels in healthy human subjects. Arosio, M., Ronchi, C.L., Beck-Peccoz, P., Gebbia, C., Giavoli, C., Cappiello, V., Conte, D., Peracchi, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  25. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. Arvat, E., Maccario, M., Di Vito, L., Broglio, F., Benso, A., Gottero, C., Papotti, M., Muccioli, G., Dieguez, C., Casanueva, F.F., Deghenghi, R., Camanni, F., Ghigo, E. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  26. Ghrelin potentiates growth hormone secretion driven by putative somatostatin withdrawal and resists inhibition by human corticotropin-releasing hormone. Veldhuis, J.D., Iranmanesh, A., Mielke, K., Miles, J.M., Carpenter, P.C., Bowers, C.Y. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  27. Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans. Vila, G., Maier, C., Riedl, M., Nowotny, P., Ludvik, B., Luger, A., Clodi, M. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  28. Regulation of ghrelin secretion and action. Camiña, J.P., Carreira, M.C., Micic, D., Pombo, M., Kelestimur, F., Dieguez, C., Casanueva, F.F. Endocrine (2003) [Pubmed]
  29. Effects of Ghrelin on growth hormone secretion from cultured adenohypophysial cells in pigs. Hashizume, T., Horiuchi, M., Tate, N., Nonaka, S., Mikami, U., Kojima, M. Domest. Anim. Endocrinol. (2003) [Pubmed]
  30. Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Pan, W., Tu, H., Kastin, A.J. Peptides (2006) [Pubmed]
  31. Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children. I??iguez, G., Salazar, T., Roman, R., Avila, A., Gunn, R.D., Cassorla, F. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  32. Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. Gaytan, F., Morales, C., Barreiro, M.L., Jeffery, P., Chopin, L.K., Herington, A.C., Casanueva, F.F., Aguilar, E., Dieguez, C., Tena-Sempere, M. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  33. Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. Arosio, M., Ronchi, C.L., Gebbia, C., Cappiello, V., Beck-Peccoz, P., Peracchi, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  34. Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. Broglio, F., Koetsveld Pv, P., Benso, A., Gottero, C., Prodam, F., Papotti, M., Muccioli, G., Gauna, C., Hofland, L., Deghenghi, R., Arvat, E., Van Der Lely, A.J., Ghigo, E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  35. Ghrelin is no longer able to stimulate growth hormone secretion in patients with Cushing's syndrome but instead induces exaggerated corticotropin and cortisol responses. Leal-Cerro, A., Torres, E., Soto, A., Dios, E., Deghenghi, R., Arvat, E., Ghigo, E., Dieguez, C., Casanueva, F.F. Neuroendocrinology (2002) [Pubmed]
  36. Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and early atherosclerosis. Ukkola, O., Pöykkö, S., Päivänsalo, M., Kesäniemi, Y.A. Ann. Med. (2008) [Pubmed]
  37. Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. Hosoda, H., Kojima, M., Mizushima, T., Shimizu, S., Kangawa, K. J. Biol. Chem. (2003) [Pubmed]
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