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Gene Review

Ghr  -  growth hormone receptor

Rattus norvegicus

Synonyms: GH receptor, Growth hormone receptor, Somatotropin receptor
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Disease relevance of Ghr


High impact information on Ghr

  • These results suggest that the mechanism for production of the rat serum GH-binding protein is by alternative splicing of the gene for the rat GH receptor [6].
  • The protein coding region of this cDNA was identical in sequence to the extracellular domain of the rat liver GH receptor up to three amino acids before the putative transmembrane domain [6].
  • Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered [7].
  • Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats [8].
  • Recent studies have demonstrated that the activated GH receptor can stimulate Stat1, a cytoplasmic transcription factor that becomes tyrosine phosphorylated and translocates to the nucleus, where it can interact with specific DNA sequences to modulate gene expression [9].

Chemical compound and disease context of Ghr


Biological context of Ghr


Anatomical context of Ghr

  • The GHR mRNA was present in follicular wall tissue and not in the oocyte, while positive immunostaining for GHR was observed in all cells of the pre-antral follicles [17].
  • Here, we used the GH-responsive rat liver cell line CWSV-1 to investigate the role of CIS and the proteasome in GH-induced GHR internalization [16].
  • When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380 [18].
  • Treatment of Hx rats with thyroid hormones (T3 + T4), via subcutaneously (sc) implanted osmotic minipumps, induced little growth and induced a small layer of GHR-positive and GHBP-positive early maturing chondrocytes [19].
  • The dual effector theory suggests that GH would act primarily on the "stem cells." However, staining with a GH receptor (GHR) antibody is found in all layers of the growth plate in rabbits and humans [19].

Associations of Ghr with chemical compounds


Physical interactions of Ghr

  • SOCS2 binds to the GH receptor and inhibits GH signaling, including attenuation of STAT5 activation [20].
  • Immunohistochemistry was used to study the ontogeny of GH receptor/binding protein (GHR/BP) and IGF-I from the 13-day-old embryo (E13) to the E19 rat fetus in the developing incisor and molar [21].
  • Digestion of covalently linked [125I]human (h) GH-receptor complexes with neuraminidase or endoglycosidase F reduced the mass of the principal hormone receptor complex from about 130 kilodaltons (kDa) to 120 and 110 kDa, respectively, suggesting that about 20% of the mass of the GH receptor of rat adipocytes consists of N-linked sialocarbohydrates [22].

Regulatory relationships of Ghr

  • CONCLUSION: The mechanism of growth hormone insensitivity induced by endotoxin was associated with down-regulated GHR mRNA expression at receptor level and up-regulated SOCS-3 mRNA expression at post-receptor level [23].
  • The finding of endotoxin inhibition of in vivo STAT5 tyrosine phosphorylation in response to a supramaximal dose of GH in the absence of a change in GH receptor abundance or total GH-stimulated JAK2 tyrosine phosphorylation provides the first demonstration of acquired postreceptor GH resistance [24].
  • Growth hormone (GH) stimulates protein synthesis in cells transfected with GH receptor complementary DNA [25].
  • These data suggest that the regulatory mechanism controlling Sm-C/IGF-I production and growth might be different from those that regulate GH receptor concentrations, with GH pulses being crucial for the maximal stimulation of Sm-C/IGF and growth, but continuous exposure to GH being required for up-regulation of liver GH receptors [26].
  • In the male rat, few GHRH-containing neurons in the arcuate nucleus (ARC) appear to express the GH receptor messenger RNA (mRNA); however, some unidentified neurons near GHRH neurons do [27].

Other interactions of Ghr

  • GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis [14].
  • IL-1 beta markedly decreased the GHR and GHBP mRNA levels (respectively, -68% and -60%, P < 0.05) [28].
  • Neither TNF-alpha nor IL-6 affected the GHR/GHBP gene expression [28].
  • The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized [14].
  • Presently, we investigate the mechanism of CIS inhibition and CIS's role in down-regulating GHR-JAK2 signaling to STAT5b in cells exposed to GH continuously [29].

Analytical, diagnostic and therapeutic context of Ghr


  1. Growth hormone-regulated intracellular signaling in UMR 106 osteosarcoma cells. Morales, O., Lindgren, U., Haldosén, L.A. J. Bone Miner. Res. (2000) [Pubmed]
  2. Tumor necrosis factor mediates hepatic growth hormone resistance during sepsis. Yumet, G., Shumate, M.L., Bryant, P., Lin, C.M., Lang, C.H., Cooney, R.N. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  3. Growth hormone receptor and IGF-I receptor immunoreactivity during orthodontic tooth movement in the prednisolone-treated rat. Ong, C.K., Joseph, B.K., Waters, M.J., Symons, A.L. The Angle orthodontist. (2001) [Pubmed]
  4. Growth hormone receptor expression in atrophying muscle fibers of rats. Casse, A.H., Desplanches, D., Mayet-Sornay, M.H., Raccurt, M., Jegou, S., Morel, G. Endocrinology (2003) [Pubmed]
  5. Growth hormone-mediated regulation of insulin-like growth factor I promoter activity in C6 glioma cells. Benbassat, C., Shoba, L.N., Newman, M., Adamo, M.L., Frank, S.J., Lowe, W.L. Endocrinology (1999) [Pubmed]
  6. The growth hormone-binding protein in rat serum is an alternatively spliced form of the rat growth hormone receptor. Baumbach, W.R., Horner, D.L., Logan, J.S. Genes Dev. (1989) [Pubmed]
  7. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. Schaefer, F., Chen, Y., Tsao, T., Nouri, P., Rabkin, R. J. Clin. Invest. (2001) [Pubmed]
  8. Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats. Le Grevès, M., Steensland, P., Le Grevès, P., Nyberg, F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Growth hormone rapidly activates rat serine protease inhibitor 2.1 gene transcription and induces a DNA-binding activity distinct from those of Stat1, -3, and -4. Thomas, M.J., Gronowski, A.M., Berry, S.A., Bergad, P.L., Rotwein, P. Mol. Cell. Biol. (1995) [Pubmed]
  10. Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis. Pazos, F., Sánchez-Franco, F., Balsa, J.A., Escalada, J., Palacios, N., Cacicedo, L. Pediatr. Res. (2000) [Pubmed]
  11. Insulin inhibits growth hormone signaling via the growth hormone receptor/JAK2/STAT5B pathway. Ji, S., Guan, R., Frank, S.J., Messina, J.L. J. Biol. Chem. (1999) [Pubmed]
  12. Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells. Slootweg, M.C., Swolin, D., Netelenbos, J.C., Isaksson, O.G., Ohlsson, C. J. Endocrinol. (1997) [Pubmed]
  13. Distinct sexual dimorphism in the effect of hypothyroidism on the expression of the growth hormone receptor and growth hormone-binding protein gene in rat liver. Romero, G.S., Stephan, D.A., Sperling, M.A., Menon, R.K. Horm. Res. (1996) [Pubmed]
  14. Renal growth hormone receptor gene expression: relationship to renal insulin-like growth factor system. Chin, E., Zhou, J., Bondy, C.A. Endocrinology (1992) [Pubmed]
  15. Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development. Cruickshank, J., Grossman, D.I., Peng, R.K., Famula, T.R., Oberbauer, A.M. J. Endocrinol. (2005) [Pubmed]
  16. Role of the cytokine-induced SH2 domain-containing protein CIS in growth hormone receptor internalization. Landsman, T., Waxman, D.J. J. Biol. Chem. (2005) [Pubmed]
  17. Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR), insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene expression of GH and GHR in rat pre-antral follicles. Zhao, J., Taverne, M.A., van der Weijden, G.C., Bevers, M.M., van den Hurk, R. Zygote (2002) [Pubmed]
  18. Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. Allevato, G., Billestrup, N., Goujon, L., Galsgaard, E.D., Norstedt, G., Postel-Vinay, M.C., Kelly, P.A., Nielsen, J.H. J. Biol. Chem. (1995) [Pubmed]
  19. Localization and regulation of the growth hormone receptor and growth hormone-binding protein in the rat growth plate. Gevers, E.F., van der Eerden, B.C., Karperien, M., Raap, A.K., Robinson, I.C., Wit, J.M. J. Bone Miner. Res. (2002) [Pubmed]
  20. SOCS2 induces neurite outgrowth by regulation of epidermal growth factor receptor activation. Goldshmit, Y., Walters, C.E., Scott, H.J., Greenhalgh, C.J., Turnley, A.M. J. Biol. Chem. (2004) [Pubmed]
  21. Prenatal expression of growth hormone receptor/binding protein and insulin-like growth factor-I (IGF-I) in the enamel organ. Role for growth hormone and IGF-I in cellular differentiation during early tooth formation? Joseph, B.K., Savage, N.W., Young, W.G., Waters, M.J. Anat. Embryol. (1994) [Pubmed]
  22. Effects of tunicamycin on growth hormone binding in rat adipocytes. Szecowka, J., Tai, L.R., Goodman, H.M. Endocrinology (1990) [Pubmed]
  23. Mechanism of growth hormone insensitivity induced by endotoxin. Wang, P., Li, N., Li, J.S. Acta Pharmacol. Sin. (2002) [Pubmed]
  24. Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo. Mao, Y., Ling, P.R., Fitzgibbons, T.P., McCowen, K.C., Frick, G.P., Bistrian, B.R., Smith, R.J. Endocrinology (1999) [Pubmed]
  25. Growth hormone (GH) stimulates protein synthesis in cells transfected with GH receptor complementary DNA. Emtner, M., Mathews, L.S., Norstedt, G. Mol. Endocrinol. (1990) [Pubmed]
  26. Different effects of intermittent and continuous growth hormone (GH) administration on serum somatomedin-C/insulin-like growth factor I and liver GH receptors in hypophysectomized rats. Maiter, D., Underwood, L.E., Maes, M., Davenport, M.L., Ketelslegers, J.M. Endocrinology (1988) [Pubmed]
  27. Regulation of hypothalamic neuropeptide-Y neurons by growth hormone in the rat. Chan, Y.Y., Steiner, R.A., Clifton, D.K. Endocrinology (1996) [Pubmed]
  28. Inhibition by interleukin-1 beta and tumor necrosis factor-alpha of the insulin-like growth factor I messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture. Thissen, J.P., Verniers, J. Endocrinology (1997) [Pubmed]
  29. Role of the cytokine-inducible SH2 protein CIS in desensitization of STAT5b signaling by continuous growth hormone. Ram, P.A., Waxman, D.J. J. Biol. Chem. (2000) [Pubmed]
  30. Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton. Rico-Bautista, E., Negrín-Martínez, C., Novoa-Mogollón, J., Fernández-Perez, L., Flores-Morales, A. Exp. Cell Res. (2004) [Pubmed]
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