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Gene Review

Ghrhr  -  growth hormone releasing hormone receptor

Mus musculus

Synonyms: GHRH receptor, GRF receptor, GRFR, Ghrfr, Grfr, ...
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Disease relevance of Ghrhr


High impact information on Ghrhr

  • We report that the Ghrhr gene is located in the middle of mouse chromosome 6 in the same region as the little mutation [5].
  • GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function [5].
  • Expression of GHRH and splice variant 1 of the GHRH receptor in both cell lines was examined by RT-PCR [6].
  • Although GHRH and its receptor (GHRHR) are expressed in leukocytes, physiological function of GHRH in the immune system remains unclear [1].
  • Splenocytes from MOG-immunized lit/lit mice proliferated normally in response to MOG peptide, suggesting that activation of MOG-specific T cells in GHRHR-deficient mice is not impaired [1].

Biological context of Ghrhr

  • No recombinations between lit and Ghrfr were detected [7].
  • The defect has been mapped to a missense mutation in the GHRH receptor gene that abolishes the function of the receptor, but the mechanism of this inactivation is unknown [8].
  • The phenotype is strikingly similar to that observed in the mouse with mutated GHRH receptor (little) [9].
  • Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus [10].
  • In addition, glucocorticoids are potent positive regulators of GHRH receptor gene expression [11].

Anatomical context of Ghrhr


Associations of Ghrhr with chemical compounds

  • Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency [15].

Other interactions of Ghrhr

  • In addition, treating primary pituitary cell cultures from lean mice with insulin reduced GH release as well as GH, GHRH receptor, and ghrelin receptor mRNA levels compared with vehicle-treated controls, where the magnitude of suppression of pituitary mRNA levels was similar to that observed in the DIO mouse [16].

Analytical, diagnostic and therapeutic context of Ghrhr

  • In this study, Western blots, using antiserum raised against the GHRH receptor and immunoprecipitation analysis of epitope-tagged receptors, demonstrate that both wild-type and mutant receptor proteins are expressed at equivalent levels in transfected cells [8].
  • Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice [17].


  1. Cutting edge: Requirement for growth hormone-releasing hormone in the development of experimental autoimmune encephalomyelitis. Ikushima, H., Kanaoka, M., Kojima, S. J. Immunol. (2003) [Pubmed]
  2. Genetically caused retarded growth in animals. Sellier, P. Domest. Anim. Endocrinol. (2000) [Pubmed]
  3. Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor. Kiaris, H., Chatzistamou, I., Schally, A.V., Halmos, G., Varga, J.L., Koutselini, H., Kalofoutis, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers. Letsch, M., Schally, A.V., Busto, R., Bajo, A.M., Varga, J.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Godfrey, P., Rahal, J.O., Beamer, W.G., Copeland, N.G., Jenkins, N.A., Mayo, K.E. Nat. Genet. (1993) [Pubmed]
  6. Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone. Keller, G., Schally, A.V., Groot, K., Toller, G.L., Havt, A., Köster, F., Armatis, P., Halmos, G., Zarandi, M., Varga, J.L., Engel, J.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse chromosome 6. Chua, S.C., Hennessey, K., Zeitler, P., Leibel, R.L. Mamm. Genome (1993) [Pubmed]
  8. The mutant growth hormone-releasing hormone (GHRH) receptor of the little mouse does not bind GHRH. Gaylinn, B.D., Dealmeida, V.I., Lyons, C.E., Wu, K.C., Mayo, K.E., Thorner, M.O. Endocrinology (1999) [Pubmed]
  9. Partial reversibility of growth hormone (GH) deficiency in the GH-releasing hormone (GHRH) knockout mouse by postnatal treatment with a GHRH analog. Alba, M., Schally, A.V., Salvatori, R. Endocrinology (2005) [Pubmed]
  10. Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh. Maheshwari, H.G., Silverman, B.L., Dupuis, J., Baumann, G. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  11. Regulation of the pituitary somatotroph cell by GHRH and its receptor. Mayo, K.E., Miller, T., DeAlmeida, V., Godfrey, P., Zheng, J., Cunha, S.R. Recent Prog. Horm. Res. (2000) [Pubmed]
  12. GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population, GH release, and responsiveness to GH-releasing factors and somatostatin. Garc??a-Tornad??, I., Rubinstein, M., Gaylinn, B.D., Hill, D., Arany, E., Low, M.J., D??az-Torga, G., Becu-Villalobos, D. J. Endocrinol. (2006) [Pubmed]
  13. Suppression of mammary-derived growth inhibitor gene expression by growth hormone and insulin-like growth factor I. Huynh, H., Beamer, W. Int. J. Oncol. (1998) [Pubmed]
  14. Pituitary hypoplasia in patients with a mutation in the growth hormone-releasing hormone receptor gene. Murray, R.A., Maheshwari, H.G., Russell, E.J., Baumann, G. AJNR. American journal of neuroradiology. (2000) [Pubmed]
  15. Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency. Maheshwari, H.G., Rahim, A., Shalet, S.M., Baumann, G. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  16. Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Luque, R.M., Kineman, R.D. Endocrinology (2006) [Pubmed]
  17. Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice. Alt, J.A., Obal, F., Traynor, T.R., Gardi, J., Majde, J.A., Krueger, J.M. J. Appl. Physiol. (2003) [Pubmed]
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