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Gene Review

GHR  -  growth hormone receptor

Gallus gallus

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Disease relevance of GHR

  • Although the actual defect in GHR gene expression in SLD Leghorns remains to be identified, this study demonstrates that sex-linked dwarfism, like Laron dwarfism, is due to a heterogeneity of lesions [1].
  • This type of dwarfism resembles Laron-type dwarfism in humans, where a defect in the GH receptor gene has recently been identified [2].
  • We examined the effect of the dwarfing gene on body weight, hepatic GH-binding activity, and the structure and expression of the growth hormone receptor (GHR) gene in two different lines of sex-linked dwarf (SLD) broiler chickens [3].

High impact information on GHR

  • In a chimeric construct, the signal and neighboring sequence from the cGHR are sufficient to confer cleavage and polyadenylation upon the rat GHR, a gene that otherwise lacks the internal poly(A) signal [4].
  • Western blotting determined the molecular size of immunoreactive GH in RPE cells to be 80-84 kDa, similar to the computed molecular mass of s-cGH/GH receptor complex [5].
  • These receptor-deficient chickens should serve as a unique model system for studying the role of the GH receptor in growth and development [2].
  • A novel complementary DNA (cDNA) encoding the chicken GH receptor was isolated from a chicken liver cDNA library, using polymerase chain reaction with primers derived from highly conserved sequences of the mammalian GH receptor [2].
  • Despite this low level of homology, a number of structural features of the GH receptor are conserved, including 7 cysteine residues in the extracellular domain and 5 in the intracellular region [2].

Biological context of GHR

  • These results demonstrate that, in contrast to broiler SLDs, a GHR gene deletion is not responsible for the GHR dysfunction in Leghorn SLDs [1].
  • These results indicate that a mutation in the GH receptor gene is responsible for the phenotype of the sex-linked dwarf chicken [2].
  • Growth hormone binding protein (GHBP) may be an important factor in the regulation of growth and might provide an indirect, relatively noninvasive means of predicting the status of hepatic growth hormone receptor (GHR) activity [6].
  • GHR cDNA was obtained from dwarf chicken liver RNA by reverse transcription-polymerase chain reaction, and nucleotide sequence analysis revealed that it contained an intron sequence of the GHR gene [7].
  • Northern and Southern blotting and PCR analysis revealed restriction fragment length polymorphism patterns and a 1.7 kb deletion of the intracellular domain of the GH receptor gene in commercial dwarf broiler chicks, similar to the Connecticut strain in which there is a dysfunctional GH receptor [8].

Anatomical context of GHR


Associations of GHR with chemical compounds

  • In the liver, the messenger RNA (mRNA) expressions both for GH receptor (GHR) and IGF-I were significantly repressed by PTU treatment, and were restored again by T4 replacement [10].
  • Hepatic inner ring deiodinating type III activity was markedly elevated, presumably as a consequence of low hepatic GH receptor numbers, and is thought to be the causal mechanism for the low plasma T3 concentrations [12].
  • Glucose is believed to be the primary trigger for the normalisation of the effects of fasting on these plasma variables by restoring hepatic GH receptor capacity, as well as decreasing deiodinase type III activity [13].

Physical interactions of GHR


Regulatory relationships of GHR

  • Thyroid hormones are involved in insulin-like growth factor-I (IGF-I) production by stimulating hepatic growth hormone receptor (GHR) gene expression in the chicken [10].

Other interactions of GHR

  • However, the analysis used only the offspring of heterozygous sires to reduce the influence of selection and genetic background (n=33 sire families for GHR; n=14 sire families for NPY; n=36 sire families for GNRHR) [14].
  • The sex-linked dwarf (dwdw) chicken represents a valuable animal model for studying GH insensitivity and the consequence of mutations in the GH receptor (GHR) gene [15].
  • We have used mRNA differential display to compare gene expression in normal and GH receptor-deficient dwarf chickens, and report here the characterization of one differentially expressed gene, which shows significant sequence identity to the sulfotransferase gene family [16].

Analytical, diagnostic and therapeutic context of GHR

  • In conclusion, the deficiency in GH receptor did not affect the male reproduction in dwarf chickens, and the fertility of dwarf cocks could be satisfactory for production when artificial insemination was adopted [17].
  • Despite the absence of hepatic GH-binding activity, Southern blot analysis shows that there is no gross structural change in the gene for the GH receptor (GHR) in this strain of dwdw chicken [18].
  • Southern and Northern blot analyses revealed different abnormalities in the GHR gene from the two separate lines of SLD [3].
  • The very sensitive competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate the expression of the extracellular (GHRe) and intracellular (GHRi) parts of the growth hormone receptor (GHR) in the liver tissue of chickens [19].
  • Effect of hypophysectomy and acute administration of growth hormone (GH) on GH-receptor binding in chick liver membranes [20].


  1. Growth hormone receptor gene expression in sex-linked dwarf Leghorn chickens: evidence against a gene deletion. Hull, K.L., Fraser, R.A., Marsh, J.A., Harvey, S. J. Endocrinol. (1993) [Pubmed]
  2. Molecular cloning of the chicken growth hormone receptor complementary deoxyribonucleic acid: mutation of the gene in sex-linked dwarf chickens. Burnside, J., Liou, S.S., Cogburn, L.A. Endocrinology (1991) [Pubmed]
  3. Abnormal growth hormone receptor gene expression in the sex-linked dwarf chicken. Burnside, J., Liou, S.S., Zhong, C., Cogburn, L.A. Gen. Comp. Endocrinol. (1992) [Pubmed]
  4. A functional polyadenylation signal is embedded in the coding region of chicken growth hormone receptor RNA. Oldham, E.R., Bingham, B., Baumbach, W.R. Mol. Endocrinol. (1993) [Pubmed]
  5. Identification of a novel GH isoform: a possible link between GH and melanocortin systems in the developing chicken eye. Takeuchi, S., Haneda, M., Teshigawara, K., Takahashi, S. Endocrinology (2001) [Pubmed]
  6. Factors affecting circulating growth hormone binding protein in chickens. Tobar-Dupres, E.T., Froman, D.P., Davis, S.L. Poult. Sci. (1993) [Pubmed]
  7. Expression of aberrantly spliced growth hormone receptor mRNA in the sex-linked dwarf chicken, Gifu 20. Tanaka, M., Hayashida, Y., Wakita, M., Hoshino, S., Nakashima, K. Growth Regul. (1995) [Pubmed]
  8. Decreased muscle cell proliferation in chicks with a deletion in the GH receptor gene. Goddard, C., Johnson, R., Gilhooley, H.J., Gardner, J.O., Gray, A., Wilkie, R.S., Butterwith, S.C. J. Mol. Endocrinol. (1996) [Pubmed]
  9. Internalization of the chicken growth hormone receptor complex and its effect on biological functions. Kühn, E.R., Vleurick, L., Edery, M., Decuypere, E., Darras, V.M. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2002) [Pubmed]
  10. Thyroid hormones are involved in insulin-like growth factor-I (IGF-I) production by stimulating hepatic growth hormone receptor (GHR) gene expression in the chicken. Tsukada, A., Ohkubo, T., Sakaguchi, K., Tanaka, M., Nakashima, K., Hayashida, Y., Wakita, M., Hoshino, S. Growth Horm. IGF Res. (1998) [Pubmed]
  11. Generation of growth hormone binding protein by avian growth plate chondrocytes is dependent on cell differentiation. Monsonego, E., Baumbach, W.R., Lavelin, I., Gertler, A., Hurwitz, S., Pines, M. Mol. Cell. Endocrinol. (1997) [Pubmed]
  12. Food deprivation and feeding of broiler chickens is associated with rapid and interdependent changes in the somatotrophic and thyrotrophic axes. Buyse, J., Decuypere, E., Darras, V.M., Vleurick, L.M., Kühn, E.R., Veldhuis, J.D. Br. Poult. Sci. (2000) [Pubmed]
  13. Pre- and postprandial changes in plasma hormone and metabolite levels and hepatic deiodinase activities in meal-fed broiler chickens. Buyse, J., Janssens, K., Van der Geyten, S., Van As, P., Decuypere, E., Darras, V.M. Br. J. Nutr. (2002) [Pubmed]
  14. A study of association between genetic markers in candidate genes and reproductive traits in one generation of a commercial broiler breeder hen population. Dunn, I.C., Miao, Y.W., Morris, A., Romanov, M.N., Wilson, P.W., Waddington, D. Heredity (2004) [Pubmed]
  15. Dysfunctional growth hormone receptor in a strain of sex-linked dwarf chicken: evidence for a mutation in the intracellular domain. Agarwal, S.K., Cogburn, L.A., Burnside, J. J. Endocrinol. (1994) [Pubmed]
  16. Cloning and expression of a novel chicken sulfotransferase cDNA regulated by GH. Cao, H., Agarwal, S.K., Burnside, J. J. Endocrinol. (1999) [Pubmed]
  17. Deficiency of growth hormone receptor does not affect male reproduction in dwarf chickens. Zheng, J.X., Liu, Z.Z., Yang, N. Poult. Sci. (2007) [Pubmed]
  18. Overexpression of a truncated growth hormone receptor in the sex-linked dwarf chicken: evidence for a splice mutation. Huang, N., Cogburn, L.A., Agarwal, S.K., Marks, H.L., Burnside, J. Mol. Endocrinol. (1993) [Pubmed]
  19. Quantification of growth hormone receptor extra- and intracellular domain gene expression in chicken liver by quantitative competitive RT-PCR. Van As, P., Janssens, W., Onagbesan, O.M., Bruggeman, V., Buys, N., Sanders, J., Van Der Geyten, S., Darras, V.M., Decuypere, E. Gen. Comp. Endocrinol. (2001) [Pubmed]
  20. Effect of hypophysectomy and acute administration of growth hormone (GH) on GH-receptor binding in chick liver membranes. Vanderpooten, A., Darras, V.M., Huybrechts, L.M., Rudas, P., Decuypere, E., Kühn, E.R. J. Endocrinol. (1991) [Pubmed]
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