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  • Title: Hepatic expression of growth hormone receptor/binding protein and insulin-like growth factor I genes in uremic rats. Influence of nutritional deficit.
    Author: Martínez V, Balbín M, Ordóñez FA, Rodríguez J, García E, Medina A, Santos F.
    Journal: Growth Horm IGF Res; 1999 Feb; 9(1):61-8. PubMed ID: 10207509.
    Abstract:
    The molecular basis for GH resistance in chronic renal failure is unknown. It may partly reside in a decreased number of hepatic GH receptors and subsequently reduced IGF-I synthesis. To investigate the hepatic expression of GH receptor/binding protein (GHBP) and IGF-I genes in chronic renal failure, mRNA levels and the concentrations of its splicing variants were measured by Northern Blot in male 5/6 nephrectomized rats (NX, n = 9), aged 26 +/- 1 days, and three groups of sham-operated rats: (1) fed ad libitum (SAL, n = 9); (2) pair-fed with NX (SPF, n = 7); and (3) pair-fed with NX in terms of protein ingestion but calorically supplemented up to the intake of SAL (SPF+, n = 8). NX rats had severe renal failure, serum urea nitrogen 106 +/- 11 mg/dl (mean +/- SEM), and were growth retarded. GH receptor/GHBP gene expression was detected as two bands of 4.7 and 1.2 kb, respectively. The amount of mRNA was lower (P < 0.0001) in NX than SAL, either when both bands were considered together or separately. No differences were found between NX, SPF, and SPF+. Serum GHBP concentrations were higher (P < 0.01) in NX rats than the other groups. For the IGF-I gene, two bands of 7.5 and 1.8-0.8 kb were identified. Expression of IGF-I gene was reduced (P < 0.05) in NX in comparison with SAL, this reduction being more marked for the 7.5 kb transcript (amount of mRNA equal to 56.6 +/- 2.6 vs 84.8 +/- 6.2% of values found in SAL rats). There were no differences between NX and SPF. Normalization of caloric intake in SPF+ resulted in partial recovery of the 7.5-kb band and did not modify the 1.8-0.8 kb mRNAs. Circulating IGF-I levels were no different among the four groups. These data confirm that expression of liver GH receptor/GHBP and IGF-I genes is markedly decreased in uremic rats. Nutritional deficiency and not uremia itself seems to be the main causal factor, with protein deficit playing a major role.
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