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.
Allan
C J
CJ
Department of Pharmacology, University of Glasgow.
Skett
P
P
D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation; D005989:Glycerides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D004075:Diglycerides; D005989:Glycerides; D000735:Androstenedione; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate