ZINC REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), GROWTH-HORMONE RECEPTOR (GHR) AND BINDING-PROTEIN (GHBP) GENE-EXPRESSION IN RAT CULTURED-HEPATOCYTES

Dietary zinc depletion in vivo attenuates growth, decreases circulatin g insulin-like growth factor-I (IGF-I) and liver growth hormone (GH) r eceptors (GHR). In order to investigate a direct role of zinc in the r egulation of IGF-I, GHR and GH binding protein (GHBP) gene expression, we evaluated the response of their mRNAs to changes in zinc availabil ity in primary culture of rat hepatocytes. Exposition of cells to the zinc chelator DTPA (diethylenetriaminepenta-acetic acid) did not decre ase IGF-I and GHBP mRNAs while it strongly inhibited metallothionein ( MT) gene expression. On the other hand, zinc excess (50 vs. 1.5 mu M) decreased IGF-I, GHR and GHBP mRNAs while it stimulated MT mRNA. Howev er, the response of IGF-I to GH was not affected by the exposure to DT PA nor zinc excess. Furthermore, zinc repletion of primary cultured he patocytes isolated from zinc-deprived rats did not increase IGF-I nor GHR/GHBP mRNAs. Therefore, our results suggest that the IGF-I decline induced in vivo by zinc deficiency is not caused by reduced extracellu lar zinc availability at the hepatocyte level. Although IGF-I and MT g ene expression is down-regulated by dietary zinc depletion, underlying mechanisms of regulation are different for both genes. (C) 1998 Elsev ier Science Ireland Ltd. All rights reserved.