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

• GH receptor (GHR) mRNA has been identified in peripheral (liver and muscle) and central (brain and hypothalamus) tissues of sex-linked dwarf (SLD) Leghorn chickens [1].
• An in vitro study using a COS-7 cell line transfected with the cDNA of the chicken GHR, revealed that GHR immunofluorescence was found in the perinuclear region and on the plasma membrane [9].
• These results indicate that thyroid hormones regulate IGF-I production in the chicken by affecting hepatic GHR expression [10].
• This study determined the consequences of GH receptor gene mutation on muscle cell proliferation in vivo [8].
• In the epiphyseal growth-plate, chondrocytes at different stages of differentiation located at the proliferative and upper hypertrophic zones express the GH-R gene [11].

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

• GH binding to its receptor leads to internalization of the GH-GHR complex to the Golgi apparatus [9].

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].

References