Hormonal regulation of heme oxygenase induction in avian hepatocyte culture.

The effects of various hormones were examined on the induction of heme oxygenase in monolayer cultures in chick embryo hepatocytes maintained in a chemically defined medium. Addition of insulin to the cultured cells markedly suppressed the activity of basal as well as Co2+-induced heme oxygenase. Treatment of cells with hydrocortisone also suppressed the basal enzyme activity, while the Co2+-induced enzyme activity was enhanced slightly. In contrast, triiodothyronine addition to the culture caused a slight increase of both uninduced and induced levels of the enzyme. This stimulatory effect of triiodothyronine was enhanced significantly by prolonged incubation of cells (48-96 hr) in the serum-free medium. These findings indicate that heme oxygenase synthesis can be substantially altered by changing the hormonal environment of the hepatocytes. Furthermore, the induction of heme oxygenase by Co2+ was inhibited by glucagon, dibutyryl cAMP and theophylline in a dose-dependent manner, suggesting that the enzyme induction may also be controlled by changes in cAMP levels.