Hepatic expression of growth hormone receptor/binding protein and insulin-like growth factor I genes in uremic rats. Influence of nutritional deficit

Growth Horm IGF Res. 1999 Feb;9(1):61-8. doi: 10.1054/ghir.1998.0088.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Gene Expression Regulation*
  • Insulin-Like Growth Factor I / genetics*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / metabolism
  • Liver / metabolism*
  • Male
  • Nutrition Disorders / complications
  • Nutrition Disorders / genetics*
  • Nutrition Disorders / metabolism
  • Protein-Energy Malnutrition / complications
  • Protein-Energy Malnutrition / genetics
  • Protein-Energy Malnutrition / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatotropin / genetics*
  • Uremia / complications
  • Uremia / genetics
  • Uremia / metabolism

Substances

  • Carrier Proteins
  • Receptors, Somatotropin
  • Insulin-Like Growth Factor I
  • somatotropin-binding protein