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

• Additionally, fasting insulin and glucose levels were reduced in the GHR -/- mice but normal in the GHA mice [18].
• Epinephrine treatment did not affect the amount of GHR 1A or IGF-I mRNA [19].
• The decrease in GHR 1A mRNA was associated with a decrease in progesterone and an increase in estradiol shortly before parturition [20].
• A RT-PCR analysis revealed that mRNA for GH receptor in CL was fully expressed from early in the luteal phase throughout the estrous cycle, while luteinizing hormone (LH) receptor mRNA was expressed less by the early and regressing CL than those at mid or late luteal phases (P < 0.05) [21].
• We have analyzed the expression of GH receptors (GHR) in murine lymphoid organs using flow cytofluorometry with biotinylated bovine GH and specific fluorescein isothiocyanate-labeled monoclonal antibodies defining distinct lymphoid cell populations [22].

Physical interactions of GHR

• Growth hormone (GH) binding and expression of GH receptor 1A mRNA in hepatic tissue of periparturient dairy cows [17].

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].

References