Effect of phorbol esters and diacylglycerol on steroid metabolism in isolated rat hepatocytes.

Hepatocytes, isolated from adult male rats and maintained in serum- and hormone-free medium, were pretreated with phorbol esters known to activate protein kinase C (4 beta-phorbol-12-myristate-13-acetate) and to be inactive in this respect (4 alpha-phorbol and its 12,13-didecanoate ester). Subsequently the cells were assayed for steroid-metabolizing capacity using androst-4-ene-3,17-dione as substrate. The active phorbol ester was seen to inhibit steroid metabolism markedly after 1 h whereas the inactive derivatives did not show this effect. The endogenous activator of protein kinase C (diacylglycerol) was also seen to inhibit steroid metabolism in a manner similar to the 4 beta-phorbol ester. Hepatic steroid metabolism is, thus, inhibited by activation of protein kinase C and this may be one of the mechanisms by which the regulatory hormones (e.g. growth hormone) affect steroid metabolism in the liver.