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Gene Review

GHRH  -  growth hormone releasing hormone

Homo sapiens

Synonyms: GHRF, GRF, Growth hormone-releasing factor, Growth hormone-releasing hormone, INN, ...
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Disease relevance of GHRH


Psychiatry related information on GHRH

  • Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation [5].
  • In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect [6].
  • After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo [7].
  • The present study therefore investigated the ability of CRH to inhibit the GH response to GHRH in eight young women with anorexia nervosa (AN) and in seven young women with eating disorders which were not otherwise specified (NOS) [8].
  • GH responses to GHRH were negatively correlated with the plasma insulin-like growth factor (IGF-I) concentrations and the severity of dementia [9].

High impact information on GHRH


Chemical compound and disease context of GHRH


Biological context of GHRH

  • In accordance with previous findings, the expression of both GHRHR and SV1 restored the sensitivity to GHRH-induced stimulation of cell proliferation, with SV1 being more potent than the GHRHR [1].
  • The presence of specific receptor proteins that bind GHRH antagonists in CAKI-1 RCC supports the view that distinct binding sites that mediate the inhibitory effect of GHRH antagonists are present on various human cancers [2].
  • Furthermore, MCF-7 cells transfected with SV1 proliferated more quickly than the controls, even in the absence of exogenously added GHRH, suggesting the existence of intrinsic, ligand-independent activity of SV1 after its transfection [1].
  • A specific GHRH antagonist blocked both binding and second messenger response [19].
  • In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h] [14].

Anatomical context of GHRH

  • A splice variant (SV) of the full-length receptor for GHRH (GHRHR) is widely expressed in various primary human cancers and established cancer cell lines and appears to mediate the proliferative effects of GHRH [1].
  • In addition, high-affinity, low-capacity binding sites for GHRH antagonists were found on the membranes of cancer cell lines such as MiaPaCa-2 that are negative for the vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptor (VPAC-R) or lines such as LNCaP that are positive for VPAC-R [20].
  • Transient expression of this cDNA in COS cells induced saturable, high affinity, GHRH-specific binding and also stimulated intracellular cAMP accumulation in response to physiological concentrations of GHRH [19].
  • GHRH is released by the hypothalamus into the portal hypophysial circulation to bind to a membrane surface receptor [GHRH receptor (GHRHR)] expressed by the somatotropic cells [21].
  • The functional and morphological changes in the pituitary gland caused by a GHRH-producing pancreatic islet cell tumor that metastasized to the pituitary and caused somatotroph hyperplasia are described [3].

Associations of GHRH with chemical compounds

  • Pituitary function was studied in detail during each phase of the study protocol by measuring hormone levels in basal conditions and after dynamic testing (GnRH, insulin tolerance test, GHRH plus arginine, TRH, and corticotropin-releasing factor; tests) [22].
  • Pyridostigmine enhanced the first GH response to GHRH with an increase in the GH release rate; second GH responses were not augmented [23].
  • Neither the responses to clonidine nor the responses to GHRH were significantly lower in depressed patients than in controls [24].
  • No change in plasma immunoreactive GHRH (IR-GHRH) occurred after TRH, glucose, insulin, or SRIH administration [15].
  • Plasma GH did not change after GH-releasing hormone (GHRH), LHRH, or L-dopa administration [15].

Physical interactions of GHRH


Enzymatic interactions of GHRH


Regulatory relationships of GHRH

  • When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas [16].
  • The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14 [32].
  • Galanin enhances both baseline and growth hormone-releasing hormone (GHRH)-induced GH secretion both in animals and in man [33].
  • Our failure to demonstrate a difference in GH response to GHRH between schizophrenics and controls would seem to indicate that GH secretory pituitary reserve is intact in young acute male schizophrenics [34].
  • These results show that antagonistic analogs of GHRH suppress the stimulatory effects of GHRH and VIP on the cAMP production of various cancer cells [35].

Other interactions of GHRH

  • This indicates the essential role of GHRH in regulation of GH secretion [36].
  • Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion [16].
  • Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans [32].
  • These findings suggest that SSTR-specific SRIH analogs may be useful in the medical therapy of GHRH-secreting bronchial carcinoids [37].
  • In group 1 (n = 7) Gal (15 micrograms/kg h i.v.) plus GHRH (1 microgram/kg i.v.) administration induced a higher GH rise (peak = 73.1 +/- 10.2 ng/mL, mean +/- SD; area under the curve (AUC) = 531.9 +/- 78.7 ng.min.mL-1) than did GHRH alone (peak = 38.9 +/- 26.5 ng/mL, p less than 0.05; AUC = 256.9 +/- 165.6 ng/mL/min-1, p less than 0.005) [38].

Analytical, diagnostic and therapeutic context of GHRH

  • All 3 mutant receptors were expressed in CHO cells, and each failed to show a cAMP response after treatment of the cells with GHRH [39].
  • RT-PCR analyses also revealed the expression of mRNA for GHRH in 13 of 15 (86%) prostatic carcinoma specimens examined [40].
  • Immunohistochemical and in situ hybridization study revealed GHRH immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells [3].
  • Gel filtration of pooled extracts from adrenal pheochromocytomas showed that the major component of the IR-CRH, IR-GHRH, IR-SRIH, and IR-PHM eluted in the position of their synthetic counterparts [41].
  • Anemic patients on chronic hemodialysis had high basal GH concentrations, an exaggerated GH response to exogenous GHRH, increased levels of IGF-1, and elevated levels of IGF-1 binding protein-3 in comparison to controls [42].


  1. Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor. Barabutis, N., Tsellou, E., Schally, A.V., Kouloheri, S., Kalofoutis, A., Kiaris, H. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  2. Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone. Halmos, G., Schally, A.V., Varga, J.L., Plonowski, A., Rekasi, Z., Czompoly, T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. A growth hormone-releasing hormone-producing pancreatic islet cell tumor metastasized to the pituitary is associated with pituitary somatotroph hyperplasia and acromegaly. Sanno, N., Teramoto, A., Osamura, R.Y., Genka, S., Katakami, H., Jin, L., Lloyd, R.V., Kovacs, K. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  4. Characterization of growth hormone-releasing hormone receptors in pituitary adenomas from patients with acromegaly. Ikuyama, S., Natori, S., Nawata, H., Kato, K., Ibayashi, H., Kariya, T., Sakai, T., Rivier, J., Vale, W. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  5. Alpha 2-adrenoceptor sensitivity in anorexia nervosa: GH response to clonidine or GHRH stimulation. Brambilla, F., Ferrari, E., Cavagnini, F., Invitti, C., Zanoboni, A., Massironi, R., Catalano, M., Cocchi, D., Müller, E.E. Biol. Psychiatry (1989) [Pubmed]
  6. Neuropeptides and human sleep. Steiger, A., Holsboer, F. Sleep. (1997) [Pubmed]
  7. Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation. Schüssler, P., Yassouridis, A., Uhr, M., Kluge, M., Weikel, J., Holsboer, F., Steiger, A. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  8. Corticotrophin-releasing hormone does not inhibit growth hormone-releasing hormone-induced release of growth hormone in control subjects but is effective in patients with eating disorders. Rolla, M., Andreoni, A., Bellitti, D., Ferdeghini, M., Ghigo, E., Müller, E.E. J. Endocrinol. (1994) [Pubmed]
  9. Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease. Lesch, K.P., Ihl, R., Frölich, L., Rupprecht, R., Müller, U., Schulte, H.M., Maurer, K. Psychiatry research. (1990) [Pubmed]
  10. Neuroendocrine control of growth hormone secretion. Müller, E.E., Locatelli, V., Cocchi, D. Physiol. Rev. (1999) [Pubmed]
  11. Acceleration of growth in two children treated with human growth hormone-releasing factor. Thorner, M.O., Reschke, J., Chitwood, J., Rogol, A.D., Furlanetto, R., Rivier, J., Vale, W., Blizzard, R.M. N. Engl. J. Med. (1985) [Pubmed]
  12. Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. Williams, T., Berelowitz, M., Joffe, S.N., Thorner, M.O., Rivier, J., Vale, W., Frohman, L.A. N. Engl. J. Med. (1984) [Pubmed]
  13. Production of growth hormone-releasing factor in pheochromocytoma. Sano, T., Saito, H., Yamazaki, R., Kameyama, K., Ikeda, M., Hosoi, E., Hizawa, K., Saito, S. N. Engl. J. Med. (1984) [Pubmed]
  14. Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. Ghigo, E., Arvat, E., Gianotti, L., Nicolosi, M., Valetto, M.R., Avagnina, S., Bellitti, D., Rolla, M., Müller, E.E., Camanni, F. Biol. Psychiatry (1994) [Pubmed]
  15. Acromegaly due to a growth hormone-releasing hormone-secreting bronchial carcinoid tumor: further information on the abnormal responsiveness of the somatotroph cells and their recovery after successful treatment. Boizel, R., Halimi, S., Labat, F., Cohen, R., Bachelot, I. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  16. Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. Ishibashi, M., Yamaji, T. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  17. Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. Doga, M., Bonadonna, S., Burattin, A., Giustina, A. Ann. Oncol. (2001) [Pubmed]
  18. Immunocytochemical localisation of plasma membrane GHRH receptors in human tumours using a novel anti-peptide antibody. Schulz, S., Röcken, C., Schulz, S. Eur. J. Cancer (2006) [Pubmed]
  19. Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Gaylinn, B.D., Harrison, J.K., Zysk, J.R., Lyons, C.E., Lynch, K.R., Thorner, M.O. Mol. Endocrinol. (1993) [Pubmed]
  20. Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers. Rekasi, Z., Czompoly, T., Schally, A.V., Halmos, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  21. Familial Growth Hormone Deficiency and Mutations in the GHRH Receptor Gene. Alba, M., Salvatori, R. Vitam. Horm. (2004) [Pubmed]
  22. Pituitary function in a man with congenital aromatase deficiency: effect of different doses of transdermal E2 on basal and stimulated pituitary hormones. Rochira, V., Balestrieri, A., Faustini-Fustini, M., Borgato, S., Beck-Peccoz, P., Carani, C. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  23. The effect of changing somatostatin tone on the pituitary growth hormone and thyroid-stimulating hormone responses to their respective releasing factor stimuli. Spoudeas, H.A., Matthews, D.R., Brook, C.G., Hindmarsh, P.C. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  24. Growth hormone response to growth hormone-releasing hormone and clonidine in depression. Gann, H., Riemann, D., Stoll, S., Berger, M., Müller, W.E. Biol. Psychiatry (1995) [Pubmed]
  25. A dominant-negative human growth hormone-releasing hormone (GHRH) receptor splice variant inhibits GHRH binding. McElvaine, A.T., Mayo, K.E. Endocrinology (2006) [Pubmed]
  26. Absence of constitutively activating mutations in the GHRH receptor in GH-producing pituitary tumors. Lee, E.J., Kotlar, T.J., Ciric, I., Lee, M.K., Lim, S.K., Lee, H.C., Huh, K.B., Mayo, K.E., Jameson, J.L. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  27. 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]
  28. The interaction of GHRH with TRH in acromegaly: a controlled study. Looij, B.J., Roelfsema, F., Frölich, M., Nieuwenhuijzen Kruseman, A.C. Acta Endocrinol. (1991) [Pubmed]
  29. Ac-Tyr1hGRF discriminates between VIP receptors from rat liver and intestinal epithelium. Rouyer-Fessard, C., Couvineau, A., Voisin, T., Laburthe, M. Life Sci. (1989) [Pubmed]
  30. Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily. Parker, D.B., Coe, I.R., Dixon, G.H., Sherwood, N.M. Eur. J. Biochem. (1993) [Pubmed]
  31. Hydrolysis of somatostatin by human tissue kallikrein after the amino acid pair phe-Phe. Pimenta, D.C., Juliano, M.A., Juliano, L. Biochem. J. (1997) [Pubmed]
  32. Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. Broglio, F., Arvat, E., Benso, A., Gottero, C., Prodam, F., Grottoli, S., Papotti, M., Muccioli, G., van der Lely, A.J., Deghenghi, R., Ghigo, E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  33. Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins, thyrotropin, adrenocorticotropin and cortisol in humans. Arvat, E., Gianotti, L., Ramunni, J., Grottoli, S., Brossa, P.C., Bertagna, A., Camanni, F., Ghigo, E. Eur. J. Endocrinol. (1995) [Pubmed]
  34. Prolactin and growth hormone responses to growth hormone-releasing hormone in acute schizophrenia. Nerozzi, D., Magnani, A., Sforza, V., Scaramucci, E., Cerilli, M., Moretti, C., Antonozzi, I., Frajese, G. Neuropsychobiology (1990) [Pubmed]
  35. Antagonistic analogs of growth hormone releasing hormone (GHRH) inhibit cyclic AMP production of human cancer cell lines in vitro. Csernus, V., Schally, A.V., Groot, K. Peptides (1999) [Pubmed]
  36. Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging. Thorner, M.O., Chapman, I.M., Gaylinn, B.D., Pezzoli, S.S., Hartman, M.L. Recent Prog. Horm. Res. (1997) [Pubmed]
  37. Somatostatin analogs in vitro effects in a growth hormone-releasing hormone-secreting bronchial carcinoid. Zatelli, M.C., Maffei, P., Piccin, D., Martini, C., Rea, F., Rubello, D., Margutti, A., Culler, M.D., Sicolo, N., degli Uberti, E.C. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  38. Evidence for involvement of endogenous somatostatin in the galanin-induced growth hormone secretion in children. Loche, S., Vista, N., Ghigo, E., Vannelli, S., Arvat, E., Benso, L., Corda, R., Cella, S.G., Müller, E.E., Pintor, C. Pediatr. Res. (1990) [Pubmed]
  39. Three new mutations in the gene for the growth hormone (gh)-releasing hormone receptor in familial isolated gh deficiency type ib. Salvatori, R., Fan, X., Phillips, J.A., Espigares-Martin, R., Martin De Lara, I., Freeman, K.L., Plotnick, L., Al-Ashwal, A., Levine, M.A. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  40. Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer. Halmos, G., Schally, A.V., Czompoly, T., Krupa, M., Varga, J.L., Rekasi, Z. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  41. Immunoreactive corticotropin-releasing hormone, growth hormone-releasing hormone, somatostatin, and peptide histidine methionine are present in adrenal pheochromocytomas, but not in extra-adrenal pheochromocytoma. Sasaki, A., Yumita, S., Kimura, S., Miura, Y., Yoshinaga, K. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  42. The effects of corticotropin and growth hormone releasing hormones on their respective secretory axes in chronic hemodialysis patients before and after correction of anemia with recombinant human erythropoietin. Ramirez, G., Bittle, P.A., Sanders, H., Rabb, H.A., Bercu, B.B. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
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