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Gene Review

Ghrhr  -  growth hormone releasing hormone receptor

Rattus norvegicus

Synonyms: GHRH receptor, GRF receptor, GRFR, Grfr, Growth hormone-releasing factor receptor, ...
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Disease relevance of Ghrhr


Psychiatry related information on Ghrhr


High impact information on Ghrhr

  • We have attempted to label the GRF receptor by chemically coupling the 125I-GRF analog [His1, Nle27]-hGRF(1-32)-NH2 (GRFa) (where Nle is norleucine) to plated rat anterior pituitary cells with the protein cross-linker disuccinimidyl suberate (DSS) (0.1 mM) [6].
  • The rat GHRH receptor mRNA is expressed predominantly, if not exclusively, in the anterior pituitary gland, the major target for GHRH action [7].
  • Finally, studies using cycloheximide and monensin showed that upon stimulation with GHRH, an optimal concentration of functional GHRH-R was maintained at the plasma membrane due to de novo synthesis and recycling in pituitary cells and to de novo synthesis solely in hGHRH-R-transfected BHK cells [8].
  • Time- and temperature-dependent internalization of stimulated GHRH-R was blocked by phenyl arsine oxide (PAO) in both cell types [8].
  • To provide information about the kidney GHRH receptor (GHRH-R), we assessed its tissue and cellular localization, defined its pattern of expression in developing and aging rats, and studied the effects of GHRH on the regulation of GHRH-R mRNA levels and receptor internalization [9].

Chemical compound and disease context of Ghrhr

  • To examine thyroid hormone regulation of the pituitary receptor for hypothalamic growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats [1].
  • Dexamethasone treatment, however, was associated with a dose-dependent reduction in weight gain (p < 0.0001) but dose-dependent increases in GHRH receptor mRNA and GH mRNA levels (p < 0.0001 and p < 0.05, respectively) [4].

Biological context of Ghrhr


Anatomical context of Ghrhr


Associations of Ghrhr with chemical compounds

  • These results suggest that the acquisition of mechanisms responsible for the regulation of GH or GHRH-receptor transcription by T3 may be involved in the process of functional development of GH cells [10].
  • On the other hand, DEX stimulated GHRH-receptor promoter alone [10].
  • Taken together, these data demonstrate that changes in the levels of pituitary GHS-R mRNA, but not GHRH-R mRNA, are associated with changes in the gonadal steroid environment, thereby implicating the GHS/GHS-R signalling system as a control point in the establishment and maintenance of sexually dimorphic patterns of GH secretion [19].
  • In MtT/E cells, DEX, RA and 9cRA showed similar effect as observed in MtT/S cells on both GH and GHRH-receptor promoter activity [10].
  • Thyroidectomy (Tx) induced a 61-65% reduction in GRF-R mRNA levels, which was significantly reversed with thyroxine (T4) replacement for 5 days at a dose of 1 microgram/100 g/day [1].

Physical interactions of Ghrhr

  • A chimera in which both the first and fourth extracellular domains of the CRF-R1 replaced the corresponding domains of the GRF-R bound astressin with Ki approximately 4 nM and urocortin with a Ki approximately 2 nM [20].
  • Functional analysis of the two GHRH receptor isoforms demonstrates that both bind GHRH, but only the short isoform signals through a cAMP-mediated pathway [3].

Regulatory relationships of Ghrhr

  • IGF-I treatment suppressed the inductive effects of T3 (P<0.02) and hydrocortisone (P<0.03) on GHRH receptor expression in adult pituitaries but not in neonatal pituitaries [21].
  • These results suggest that GHRH may regulate feeding through pituitary and/or hypothalamic GHRH receptor mechanisms [22].

Other interactions of Ghrhr


Analytical, diagnostic and therapeutic context of Ghrhr


  1. Thyroid hormone regulation of gene expression of the pituitary growth hormone-releasing factor receptor. Miki, N., Ono, M., Murata, Y., Ohsaki, E., Tamitsu, K., Ri, T., Demura, H., Yamada, M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  2. Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats. Ferrando, S., Rodríguez, J., Santos, F., Weruaga, A., Fernández, M., Carbajo, E., García, E. Kidney Int. (2002) [Pubmed]
  3. The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties. Miller, T.L., Godfrey, P.A., Dealmeida, V.I., Mayo, K.E. Endocrinology (1999) [Pubmed]
  4. Gene expression of the receptor for growth-hormone-releasing hormone is physiologically regulated by glucocorticoids and estrogen. Lam, K.S., Lee, M.F., Tam, S.P., Srivastava, G. Neuroendocrinology (1996) [Pubmed]
  5. Increased pituitary growth hormone-releasing factor (GRF) receptor messenger ribonucleic acid expression in food-deprived rats. Sugihara, H., Emoto, N., Shibasaki, T., Minami, S., Wakabayashi, I. Brain Res. (1996) [Pubmed]
  6. Cross-linking of a growth hormone releasing factor-binding protein in anterior pituitary cells. Zysk, J.R., Cronin, M.J., Anderson, J.M., Thorner, M.O. J. Biol. Chem. (1986) [Pubmed]
  7. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mayo, K.E. Mol. Endocrinol. (1992) [Pubmed]
  8. Internalization and trafficking of the human and rat growth hormone-releasing hormone receptor. Veyrat-Durebex, C., Pomerleau, L., Langlois, D., Gaudreau, P. J. Cell. Physiol. (2005) [Pubmed]
  9. Localization and regulation of a functional GHRH receptor in the rat renal medulla. Boisvert, C., Paré, C., Veyrat-Durebex, C., Robert, A., Dubuisson, S., Morel, G., Gaudreau, P. Endocrinology (2002) [Pubmed]
  10. Regulation of 5'-Promoter Activity of the Rat Growth Hormone and Growth Hormone-Releasing Hormone Receptor Genes in the MtT/S and MtT/E Cells. Nogami, H., Hiraoka, Y., Inoue, K., Aiso, S., Hisano, S. Neuroendocrinology (2006) [Pubmed]
  11. The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids. Nogami, H., Hiraoka, Y., Ogasawara, K., Aiso, S., Hisano, S. J. Mol. Endocrinol. (2005) [Pubmed]
  12. Effects of aging and dietary restriction on mRNA levels of receptors for growth hormone-releasing hormone and somatostatin in the rat pituitary. Shimokawa, I., Yanagihara, K., Higami, Y., Okimoto, T., Tomita, M., Ikeda, T., Lee, S. J. Gerontol. A Biol. Sci. Med. Sci. (2000) [Pubmed]
  13. Homologous down-regulation of growth hormone-releasing hormone receptor messenger ribonucleic acid levels. Aleppo, G., Moskal, S.F., De Grandis, P.A., Kineman, R.D., Frohman, L.A. Endocrinology (1997) [Pubmed]
  14. GH mRNA levels are elevated by forskolin but not GH releasing hormone in GHRH receptor-expressing MtT/S somatotroph cell line. Voss, T.C., Goldman, L.R., Seek, S.L., Miller, T.L., Mayo, K.E., Somogyvari-Vigh, A., Arimura, A., Hurley, D.L. Mol. Cell. Endocrinol. (2001) [Pubmed]
  15. Sleep loss alters hypothalamic growth hormone-releasing hormone receptors in rats. Gardi, J., Taishi, P., Speth, R., Obal, F., Krueger, J.M. Neurosci. Lett. (2002) [Pubmed]
  16. Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation. Moretti, C., Bagnato, A., Solan, N., Frajese, G., Catt, K.J. Endocrinology (1990) [Pubmed]
  17. Regional distribution of growth hormone-releasing hormone (GHRH) receptor mRNA in the rat brain. Takahashi, T., Okimura, Y., Yoshimura, K., Shigeyoshi, Y., Kaji, H., Abe, H., Chihara, K. Endocrinology (1995) [Pubmed]
  18. Stimulation of mitogen-activated protein kinase pathway in rat somatotrophs by growth hormone-releasing hormone. Zeitler, P., Siriwardana, G. Endocrine (2000) [Pubmed]
  19. Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats. Kamegai, J., Wakabayashi, I., Kineman, R.D., Frohman, L.A. J. Neuroendocrinol. (1999) [Pubmed]
  20. The first extracellular domain of corticotropin releasing factor-R1 contains major binding determinants for urocortin and astressin. Perrin, M.H., Sutton, S., Bain, D.L., Berggren, W.T., Vale, W.W. Endocrinology (1998) [Pubmed]
  21. Regulation of GHRH receptor gene expression in the neonatal and adult rat pituitary. Korytko, A.I., Cuttler, L. Growth Horm. IGF Res. (2001) [Pubmed]
  22. Effects of peripheral and central administration of GHRH on feeding in aging LOU rats. Veyrat-Durebex, C., Gaudreau, P., Boghossian, S., Alliot, J. Peptides (2001) [Pubmed]
  23. Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. Tam, S.P., Lam, K.S., Srivastava, G. Endocrinology (1996) [Pubmed]
  24. The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of the GH gene in vitro. Morishita, M., Iwasaki, Y., Onishi, A., Asai, M., Mutsuga, N., Yoshida, M., Oiso, Y., Inoue, K., Murohara, T. J. Mol. Endocrinol. (2003) [Pubmed]
  25. Growth hormone (GH)-releasing hormone (GHRH) and the GH secretagogue (GHS), L692,585, differentially modulate rat pituitary GHS receptor and GHRH receptor messenger ribonucleic acid levels. Kineman, R.D., Kamegai, J., Frohman, L.A. Endocrinology (1999) [Pubmed]
  26. Synthesis and biological activity of novel C-terminal-extended and biotinylated growth hormone-releasing factor (GRF) analogs. Campbell, R.M., Lee, Y., Mowles, T.F., McIntyre, K.W., Ahmad, M., Felix, A.M., Heimer, E.P. Peptides (1992) [Pubmed]
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