Zinc supplementation selectively decreases fetal hepatocyte DNA synthesis and insulin-like growth factor II gene expression in primary culture.
Zinc is important for normal cell growth and differentiation, DNA synthesis, and gene expression. IGF-II is a fetal growth and differentiation factor whose regulation is largely unknown. To assess the effect of zinc (Zn) on fetal hepatocyte IGF-II expression and DNA synthesis, primary cultures of ovine fetal hepatocytes were studied in serum-free medium containing 1 mumol/L Zn or supplemented to 10 or 50 mumol/L Zn. Fetal hepatocyte DNA synthesis, Zn and protein content, IGF-II mRNA, and IGF binding protein production were measured. Zn concentration in medium increased slightly in unsupplemented dishes, from 1 to 1.5 mumol/L; however, Zn concentration declined by 4 and 8 mumol/L over 24 h in culture medium supplemented to contain either 10 or 50 mumol/L Zn (p < 0.05). Zn content of cell pellets increased 155 and 204% after 24 h in supplemented cultures compared with unsupplemented controls, demonstrating uptake of Zn by the liver cells. Media Zn supplementation to 10 and 50 mumol/L decreased 3H-thymidine incorporation of cells in culture by 11 and 13%, respectively, compared with 1 mumol/L Zn (p = 0.001). Addition of Zn caused a progressive 2- to 3-fold decline in the nuclear labeling index of fetal hepatocytes, whereas the labeling index of nonhepatocytes increased almost 2-fold at 50 mumol/L compared with 1 mumol/L Zn. Associated with decreased hepatocyte DNA synthesis, IGF-II mRNA abundance declined by almost 30%. IGF binding protein content of conditioned medium did not change with added Zn.(ABSTRACT TRUNCATED AT 250 WORDS)
Townsend
S F
SF
Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262.
Briggs
K K
KK
Krebs
N F
NF
Hambidge
K M
KM
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000196:embryology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012756:Sheep / Q000196:embryology; D015032:Zinc / Q000494:pharmacology*
D005326:Fetal Proteins; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D015032:Zinc