Differential regulation of insulin-like growth factor I (IGF-I) and IGF binding protein-1 messenger ribonucleic acids by amino acid availability and growth hormone in rat hepatocyte primary culture

Endocrinology. 1994 Mar;134(3):1570-6. doi: 10.1210/endo.134.3.7509741.


To determine the mechanisms involved in the nutritional regulation of insulin-like growth factor I (IGF-I) production and action, we studied the regulation of IGF-I and IGF-Binding Protein 1 (IGFBP-1) gene expression by GH and amino acid availability in rat hepatocyte primary culture. Hepatocytes were isolated by in situ collagenase perfusion and cultured on Matrigel in serum-free medium containing insulin and hydrocortisone. Rat GH (500 ng/ml) increased IGF-I messenger RNA (mRNA) abundance 6.9-fold at 24 h, as measured by Northern Blot using an IGF-I-specific riboprobe. In contrast, IGFBP-1 mRNA levels were decreased by 41% after 24 h of rat GH treatment. Hepatocytes were incubated for 24 h in three media differing in their amino acid concentrations: 0.2X, 1X, and 5X the normal rat plasma concentration. Amino acid deprivation (0.2X) decreased the abundance of IGF-I mRNAs (-56% after 24 h), whereas amino acid excess (5X) increased it (+70%) in comparison to the 1X medium. In contrast, amino acid deprivation increased IGFBP-1 mRNA abundance (+69%), whereas excess decreased it (-75%). Studies of the interaction between GH and amino acids, accomplished by the simultaneous manipulation of the two, suggest that each factor modulates the IGF-I mRNA and the IGFBP-1 mRNA and protein response to the other. We conclude that the IGF-I and IGFBP-1 genes are regulated in opposite ways by GH and amino acid availability. Our observations suggest that amino acids and GH regulate the production of IGF-I directly and exert indirect effects on IGF-I action by regulating the production of IGFBP-1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Carrier Proteins / genetics*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation* / drug effects
  • Growth Hormone / pharmacology
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / analysis*
  • Rats
  • Rats, Sprague-Dawley


  • Amino Acids
  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Growth Hormone