Disease relevance of GHR

• During mild postnatal undernutrition, growth hormone receptor (GHR) mRNA abundance decreases in liver but increases in longissimus dorsi muscle [1].
• However, fetal hypothyroidism at 110F resulted in a marked 70% decrease in hepatic GHR mRNA (p < 0.01) [2].

High impact information on GHR

• The role of energy intake in regulating growth hormone receptor (GHR) gene expression has been assessed in young growing pigs living at thermal neutrality (26 degrees C) for a 4-wk period [3].
• The changes in hepatic GHR mRNA may have been driven in part by nutritionally induced changes in thyroid status, because both plasma 3,5,3'-triiodothyronine concentration and liver 5'-deiodinase activity were greater on the high than the low intake diet (P < 0.001) [3].
• Results were tissue-specific: the level of GHR mRNA per unit total RNA in liver was greater on high than low (high = 2 x low) food intake (P < 0.001), whereas in muscle it was elevated on the low compared with the high intake diet (P < 0.02) and also at 10 degrees C compared with 26 degrees C (P < 0.04) [3].
• Levels of liver GHR mRNA probably had a direct influence on growth of the animals, as they were positively correlated with plasma IGF-I and growth rate (P < 0.001), whereas muscle GHR mRNA may have had a metabolic role when energy supplies were limited [3].
• This suggests that pp95 induced by GH may be mediated by GHR dimerization and can be inhibited by overexpression of truncated porcine GHRs [4].

Biological context of GHR

• A control mAb recognizing a GHR epitope distal from its binding site for GH failed to produce the growth in rats [5].
• In situ hybridization mapping of the growth hormone receptor (GHR) gene assigns a linkage group (C9, FS, GHR, and S0105) to chromosome 16 in pigs [6].
• The GHR 1A mRNA increased after 42 d of age and tended to undergo specific down-regulation in response to rpST in pregnant gilts [7].
• The present study was conducted to determine the influence of food restriction on growth hormone receptor (GHR) in porcine skeletal muscle (longissimus dorsi and trapezius) and liver in relationship to plasma growth hormone binding protein (GHBP) [8].
• One class of chicken GHR cDNA, resulting from alternative use of a splice acceptor 17 bases upstream of the intron 6/Exon 7 junction, is also presented [9].

Anatomical context of GHR

• CONCLUSION: Collectively, dietary insulin increased mRNA levels of insulin and GH receptor, which could help explain the effect of dietary insulin on receptor-mediated postnatal development of the small intestine [10].
• Compared with group M, piglets in group MI exhibited significantly increased expression levels of both insulin and GH receptor in the ileum, and LAP in the jejunum (p<0.05); IGF-I receptor expression levels in both the jejunum and ileum were significantly decreased (p<0.01 and p<0.05, respectively), while IGF-I expression was unchanged (p>0.05) [10].
• Liver expressed GHR 1A and GHR 1B mRNA, whereas muscle, uterus, and ovary expressed GHR 1B mRNA [7].
• The expression of GH receptor mRNA was studied in oocytes and cumulus cells of the two species using reverse transcription-polymerase chain reaction with specific primers [11].
• Similar association constants were obtained for liver membrane GHR (0.79 +/- 0.22 x 10(9) M(-1)) and cytosol GHBPs (0.99 +/- 0.15 x 10(9) M(-1)), but the capacity, when expressed as femtomoles per g tissue, was significantly increased (4-fold) in cytosol (4,303 +/- 505) over that in membranes (1,071 +/- 257) [12].

Associations of GHR with chemical compounds

• The effects of glucose on GHR and IGF-I expression were dose-dependent, appearing to plateau at approximately 1-2 g/L (P = 0.031, for quadratic trend) [13].
• The stimulatory effect of some of these amino acids (arginine, proline, threonine and tryptophan) was dose-dependent for expression of class 1 transcripts of IGF-I (P = 0. 041, 0.022, 0.016 and 0.097, respectively, for linear trends), but there was no effect on GHR or class 2 transcripts of IGF-I [13].
• Removal of arginine, proline, threonine, tryptophan or valine inhibited the stimulation of IGF-I expression that was induced by the combination of T3, DEX and GH (to 15, 6, 11, 16 and 16% of control, respectively, P < 0.05), with significant decreases in GHR expression also observed in some cases [13].
• Functionally distinct muscles were assessed for GHR mRNA (RNase protection analysis), oxidative myofibers (succinate dehydrogenase histochemistry) and type I slow myofibers (myosin immunocytochemistry) [1].
• For example, histidine-168 and tyrosine-332 equivalent to positions 170 and 333 in other mammalian GHRs, which were considered to be necessary for the dimerization of GHR and the specific GH-stimulated functions respectively, were replaced by tyrosine and serine in gpGHR [14].

Regulatory relationships of GHR

• Leptin exhibited a dose-dependent stimulatory effect on GH secretion by PBMCs and also up-regulated the GH receptor gene expression [15].

Other interactions of GHR

• Effect of growth hormone (GH) on in vitro nuclear and cytoplasmic oocyte maturation, cumulus expansion, hyaluronan synthases, and connexins 32 and 43 expression, and GH receptor messenger RNA expression in equine and porcine species [11].
• In the kidney, IGFs, IGFBP-3, IGFI-R and IGFII-R as well as GHR mRNA levels were relatively high during the fetal and early postnatal life [16].
• Ontogeny of mRNA levels of IGFs, IGF type I and type II receptors (IGFI-R and IGFII-R), IGFBP-1 and -3 (IGFBPs) and growth hormone receptor (GHR) were also examined by Northern blot analysis in liver, kidney and skeletal muscle of pig [16].
• Liver RNA was analyzed for mRNAs specific for the GH receptor, IGF-1, IGF-2, and IGF binding protein 3 [17].

Analytical, diagnostic and therapeutic context of GHR

• In a radioimmunoassay, 2C3 was found to compete with iodinated porcine GH (pGH) tracer for the binding to GHR, suggesting that GHR binding sites for pGH and 2C3 were identical or closely adjacent [5].
• We therefore determined the expression of growth hormone (GH) receptor (GHR), and insulin-like growth factors I and II (IGF-I and IGF-II) mRNA in liver and skeletal muscle (longissimus) of neonatal pigs given daily intramuscular injections of either recombinant porcine GH (1 mg/kg body wt; n = 6) or saline (n = 5) for 7 days [18].
• A significant finding was that P-band is unable to bind to the pig liver-membrane GH receptor in a competitive radioreceptor assay [19].

References