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 circulating insulin-like growth factor-I (IGF-I) and liver growth hormone (GH) receptors (GHR). In order to investigate a direct role of zinc in the regulation of IGF-I, GHR and GH binding protein (GHBP) gene expression, we evaluated the response of their mRNAs to changes in zinc availability in primary culture of rat hepatocytes. Exposition of cells to the zinc chelator DTPA (diethylenetriaminepenta-acetic acid) did not decrease IGF-I and GHBP mRNAs while it strongly inhibited metallothionein (MT) gene expression. On the other hand, zinc excess (50 vs. 1.5 microM) decreased IGF-I, GHR and GHBP mRNAs while it stimulated MT mRNA. However, the response of IGF-I to GH was not affected by the exposure to DTPA nor zinc excess. Furthermore, zinc repletion of primary cultured hepatocytes 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 extracellular zinc availability at the hepatocyte level. Although IGF-I and MT gene expression is down-regulated by dietary zinc depletion, underlying mechanisms of regulation are different for both genes.
Lefebvre
D
D
Diabetes and Nutrition Unit, School of Medicine, University of Louvain, Belgium.
Beckers
F
F
Ketelslegers
J M
JM
Thissen
J P
JP
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D007797:Laminin; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D004369:Pentetic Acid / Q000494:pharmacology; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology*
D002352:Carrier Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; C059485:matrigel; D007334:Insulin-Like Growth Factor I; D004369:Pentetic Acid; D013006:Growth Hormone; D003094:Collagen; D008668:Metallothionein; D015032:Zinc; C051815:somatotropin-binding protein