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Gene Review

GHR  -  growth hormone receptor

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Disease relevance of GHR

  • The effects of substituting L allele for S allele of GHR microsatellite across Nellore, Canchim and 1/2 Angus were significant for weight gain and body weight (P < 0.05) [1].
  • The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats [2].
  • In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue [3].
  • In this study, we measured mRNA levels of 11betaHSD1 and GS in skeletal muscle of GH receptor gene disrupted (GHR-/-) mice and of their age-matched wild-type mice controls to elucidate the physiological significance of 11betaHSD1 and GC in the development of GHD-associated muscle atrophy in vivo [4].
  • For bGH mice, the increase in adipose tissue was relatively small, compared with the WT or GHR(-/-) mice, suggesting some resiliency, although not immunity, to diet-induced obesity [5].

Psychiatry related information on GHR

  • Food deprivation did not affect the levels of two other major GHR mRNA variants, 1B and 1C2, in the liver [6].

High impact information on GHR

  • To study GHR-related signaling events in these cells, protein tyrosine phosphorylation was examined [7].
  • The granulocyte colony-stimulating factor receptor (G-CSF-R) and growth hormone receptor (GH-R) belong to the cytokine receptor family and have some similarity in the cytokine receptor-homologous (CRH) domain of the extracellular region [8].
  • The use of alternative promoters represents an important mechanism for the regulation of growth hormone receptor (GHR) gene expression [9].
  • In non-hepatic tissues such as kidney, skeletal muscle, mammary gland, and uterus, P3-transcribed GHR mRNA represented 30-40% of the total GHR mRNA pool [9].
  • This is different from the closely related GH receptor that requires only the phenyl-alanine-containing motif for endocytosis [10].

Biological context of GHR

  • Transfection of a dominant negative form of AKT (AH-AKT) resulted in suppression of IGF-I-mediated cell survival, but not of the antiapoptotic effect of GH in Ba/F3 GHR cells [11].
  • Ba/F3 cells expressing the rat GH receptor (Ba/F3 GHR cells) have been shown to escape from apoptosis and to proliferate under GH stimulation [11].
  • Inhibition of nuclear factor-kappaB through expression of the mutant IkappaBalpha (A32/36) abrogated the GH-mediated survival signal, but did not result in alterations of the cell cycle in Ba/F3 GHR cells treated with IGF-I [11].
  • Maternal hepatic GHR gene expression was not affected by treatment [12].
  • A decrease in total GHR mRNA at parturition (P < 0.01) was associated with a specific decrease in GHR 1A mRNA (P < 0.001) [13].

Anatomical context of GHR

  • Insulin also doubled GHR abundance in adipose tissue (P < 0.01), indicating that this effect is not liver specific [14].
  • The aim of this study was to investigate whether bovine cumulus oocyte complexes (COCs) contain growth hormone receptor (GHR), and whether the stimulatory effect of GH on oocyte maturation is cumulus-dependent and mediated by insulin-like-growth factor (IGF-I) [15].
  • PCR on cDNA of mural granulosa cells, cumulus cells, and oocytes revealed that mRNA for GHR was present in all cell types [15].
  • Cotransfection analyses demonstrated that they also did not differ in activation by hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 4gamma and nuclear receptor subfamily 2 group F member 2, known transcription factors for bovine GHR 1A promoter [16].
  • Liver GHR 1A mRNA, specific 125I-bGH binding to liver membranes, liver IGF-I mRNA, and plasma IGF-I concentrations were lower on d 3 relative to d -12 [17].

Associations of GHR with chemical compounds


Physical interactions of GHR


Regulatory relationships of GHR

  • In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield [23].
  • These results together identify COUP-TFII, HNF-4gamma and HNF-4alpha as transcription factors regulating GHR 1A promoter activity through binding to a common DNA element [24].
  • In contrast, the expression for IGFBP-1 was upregulated in the mammary gland of virgin heifers and increased around the onset of lactation. mRNA for GHR was found during all stages examined without outstanding fluctuations [25].

Other interactions of GHR

  • These results demonstrate that the food deprivation-induced decrease in circulating IGF-I in steers is associated with a coordinate decrease in the expression of different IGF-I mRNA variants and a specific decrease in the expression of GHR mRNA variants 1C3 and 1A in the liver [6].
  • The results provide strong evidence that the effect of PRLR S18N polymorphism is distinct from the GHR F279Y effect [23].
  • The presence of IGF II, IGF-IR, GHR, IR and IGFBP-1, -2 and -3 mRNA was confirmed in the liver of 8-d old calves and older cattle as well, and among newborn calves their presence was independent of differences in nutrition [26].
  • Whereas DGAT1, GHR, and CSN1S1 polymorphisms showed association with some traits in individual populations, the lack of consistent predictive merit between populations indicates they may not be suited for beef cattle selection [27].
  • These interactions also appeared to exist in vivo, as the GHR 1A promoter containing the -196/-178 region could be recovered by immunoprecipitation of the bovine liver chromatin with antibody against COUP-TFII, HNF-4gamma or HNF-4alpha [24].

Analytical, diagnostic and therapeutic context of GHR

  • The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level found in liver from untreated, age-matched rats [2].
  • GHR(-/-) mice, which are relatively obese on a low-fat diet, responded to the dietary challenge in a manner similar to WT controls [5].
  • Nonradioactive in situ hybridization revealed that distribution of the mRNA encoding GHR was correlated with the developmental stage of the follicle [28].
  • Colocalization of the protein by immunohistochemistry showed an identical distribution pattern of GHR in 30- to 70-day-old embryos [29].
  • At the tissue level, the action of GH is mediated by the GH receptor (GHR) and the receptor-activated intracellular signaling pathway involving Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) [30].


  1. Effects of polymorphic microsatellites in the regulatory region of IGF1 and GHR on growth and carcass traits in beef cattle. Curi, R.A., Oliveira, H.N., Silveira, A.C., Lopes, C.R. Anim. Genet. (2005) [Pubmed]
  2. Decreased expression of the growth hormone receptor and growth hormone binding protein in rat liver nodules. Levinovitz, A., Husman, B., Eriksson, L.C., Norstedt, G., Andersson, G. Mol. Carcinog. (1990) [Pubmed]
  3. Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A. Butler, S.T., Marr, A.L., Pelton, S.H., Radcliff, R.P., Lucy, M.C., Butler, W.R. J. Endocrinol. (2003) [Pubmed]
  4. Lack of contribution of 11betaHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action. Itoh, E., Iida, K., Kim, D.S., Del Rincon, J.P., Coschigano, K.T., Kopchick, J.J., Thorner, M.O. Growth Horm. IGF Res. (2004) [Pubmed]
  5. Effect of growth hormone on susceptibility to diet-induced obesity. Berryman, D.E., List, E.O., Kohn, D.T., Coschigano, K.T., Seeley, R.J., Kopchick, J.J. Endocrinology (2006) [Pubmed]
  6. Reduced serum insulin-like growth factor (IGF) I is associated with reduced liver IGF-I mRNA and liver growth hormone receptor mRNA in food-deprived cattle. Wang, Y., Eleswarapu, S., Beal, W.E., Swecker, W.S., Akers, R.M., Jiang, H. J. Nutr. (2003) [Pubmed]
  7. Growth hormone (GH) induces tyrosine-phosphorylated proteins in mouse L cells that express recombinant GH receptors. Wang, X., Xu, B., Souza, S.C., Kopchick, J.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Signal transduction mediated by growth hormone receptor and its chimeric molecules with the granulocyte colony-stimulating factor receptor. Ishizaka-Ikeda, E., Fukunaga, R., Wood, W.I., Goeddel, D.V., Nagata, S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Isolation and characterization of a novel promoter for the bovine growth hormone receptor gene. Jiang, H., Okamura, C.S., Lucy, M.C. J. Biol. Chem. (1999) [Pubmed]
  10. Multiple internalization motifs differentially used by prolactin receptor isoforms mediate similar endocytic pathways. Lu, J.C., Scott, P., Strous, G.J., Schuler, L.A. Mol. Endocrinol. (2002) [Pubmed]
  11. The proliferative and antiapoptotic actions of growth hormone and insulin-like growth factor-1 are mediated through distinct signaling pathways in the Pro-B Ba/F3 cell line. Baixeras, E., Jeay, S., Kelly, P.A., Postel-Vinay, M.C. Endocrinology (2001) [Pubmed]
  12. Differential effects of maternal ovine placental lactogen and growth hormone (GH) administration on GH receptor, insulin-like growth factor (IGF)-1 and IGF binding protein-3 gene expression in the pregnant and fetal sheep. Currie, M.J., Bassett, N.S., Breier, B.H., Klempt, M., Min, S.H., Mackenzie, D.D., McCutcheon, S.N., Gluckman, P.D. Growth Regul. (1996) [Pubmed]
  13. Reduced growth hormone receptor (GHR) messenger ribonucleic acid in liver of periparturient cattle is caused by a specific down-regulation of GHR 1A that is associated with decreased insulin-like growth factor I. Kobayashi, Y., Boyd, C.K., Bracken, C.J., Lamberson, W.R., Keisler, D.H., Lucy, M.C. Endocrinology (1999) [Pubmed]
  14. Insulin increases the abundance of the growth hormone receptor in liver and adipose tissue of periparturient dairy cows. Rhoads, R.P., Kim, J.W., Leury, B.J., Baumgard, L.H., Segoale, N., Frank, S.J., Bauman, D.E., Boisclair, Y.R. J. Nutr. (2004) [Pubmed]
  15. Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF-I. Izadyar, F., Van Tol, H.T., Colenbrander, B., Bevers, M.M. Mol. Reprod. Dev. (1997) [Pubmed]
  16. Trait-associated sequence variation in the bovine growth hormone receptor 1A promoter does not affect promoter activity in vitro. Zhou, Y., Jiang, H. Anim. Genet. (2005) [Pubmed]
  17. Growth hormone (GH) binding and expression of GH receptor 1A mRNA in hepatic tissue of periparturient dairy cows. Radcliff, R.P., McCormack, B.L., Crooker, B.A., Lucy, M.C. J. Dairy Sci. (2003) [Pubmed]
  18. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Coschigano, K.T., Holland, A.N., Riders, M.E., List, E.O., Flyvbjerg, A., Kopchick, J.J. Endocrinology (2003) [Pubmed]
  19. Reduced insulin-like growth factor-I after acute feed restriction in lactating dairy cows is independent of changes in growth hormone receptor 1A mRNA. Kobayashi, Y., Boyd, C.K., McCormack, B.L., Lucy, M.C. J. Dairy Sci. (2002) [Pubmed]
  20. Plasma hormones and expression of growth hormone receptor and insulin-like growth factor-I mRNA in hepatic tissue of periparturient dairy cows. Radcliff, R.P., McCormack, B.L., Crooker, B.A., Lucy, M.C. J. Dairy Sci. (2003) [Pubmed]
  21. Growth hormone, but not luteinizing hormone, acts with luteal peptides on prostaglandin F2alpha and progesterone secretion by bovine corpora lutea in vitro. Kobayashi, S., Miyamoto, A., Berisha, B., Schams, D. Prostaglandins Other Lipid Mediat. (2001) [Pubmed]
  22. Expression of growth hormone receptors in murine lymphoid cells analyzed by flow cytofluorometry. Gagnerault, M.C., Postel-Vinay, M.C., Dardenne, M. Endocrinology (1996) [Pubmed]
  23. The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle. Viitala, S., Szyda, J., Blott, S., Schulman, N., Lidauer, M., Mäki-Tanila, A., Georges, M., Vilkki, J. Genetics (2006) [Pubmed]
  24. Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and hepatocyte nuclear factor 4gamma (HNF-4gamma) and HNF-4alpha regulate the bovine growth hormone receptor 1A promoter through a common DNA element. Xu, Q., Walther, N., Jiang, H. J. Mol. Endocrinol. (2004) [Pubmed]
  25. The expression of the IGF family and GH receptor in the bovine mammary gland. Plath-Gabler, A., Gabler, C., Sinowatz, F., Berisha, B., Schams, D. J. Endocrinol. (2001) [Pubmed]
  26. mRNA of insulin-like growth factor (IGF) quantification and presence of IGF binding proteins, and receptors for growth hormone, IGF-I and insulin, determined by reverse transcribed polymerase chain reaction, in the liver of growing and mature male cattle. Cordano, P., Hammon, H.M., Morel, C., Zurbriggen, A., Blum, J.W. Domest. Anim. Endocrinol. (2000) [Pubmed]
  27. Evaluation in beef cattle of six deoxyribonucleic acid markers developed for dairy traits reveals an osteopontin polymorphism associated with postweaning growth. White, S.N., Casas, E., Allan, M.F., Keele, J.W., Snelling, W.M., Wheeler, T.L., Shackelford, S.D., Koohmaraie, M., Smith, T.P. J. Anim. Sci. (2007) [Pubmed]
  28. Developmental changes in the expression of the growth hormone receptor messenger ribonucleic acid and protein in the bovine ovary. Kölle, S., Sinowatz, F., Boie, G., Lincoln, D. Biol. Reprod. (1998) [Pubmed]
  29. Topography of growth hormone receptor expression in the bovine embryo. Kölle, S., Sinowatz, F., Boie, G., Lincoln, D., Palma, G., Stojkovic, M., Wolf, E. Histochem. Cell Biol. (1998) [Pubmed]
  30. Short communication: A milk trait-associated polymorphism in the bovine growth hormone receptor gene does not affect receptor signaling. Zhou, Y., Jiang, H. J. Dairy Sci. (2006) [Pubmed]
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