Testosterone effect on insulin content, messenger ribonucleic acid levels,promoter activity, and secretion in the rat

Coexistence of hyperinsulinemia and hyperandrogenism in women has been freq uently described. Most of the studies addressing this issue have focused on the mechanisms by which insulin produces hyperandrogenism. In the present study, we analyzed the effects of testosterone in vivo and in vitro upon in sulin gene expression and release in the rat. Our studies demonstrate that testosterone increases insulin messenger RNA (mRNA) levels in vitro as well as in vivo. In both prepuberal and intact adult rats, serum testosterone c oncentrations were positively correlated with insulin mRNA levels and insul in concentration in serum. Testosterone deprivation after gonadectomy decre ased both insulin gene expression and serum insulin concentration. Insulin mRNA levels were partially restored after 3 days of testosterone administra tion and serum insulin was 80% and 27% above baseline values at 5 and 7 day s posttreatment. Primary cultured pancreatic islets treated with the sexual steroid increased about 80% insulin mRNA, as well as protein, and release. In transfected islets, testosterone increased the activity of the -410 bp rat insulin promoter 1 by 154%. These data demonstrate that testosterone ha s a direct effect upon pancreatic islet function by favoring insulin gene e xpression and release.