Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid.
In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4 beta-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17 beta-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells.
D000315:Adrenalectomy; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009955:Ornithine Decarboxylase / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D007328:Insulin; D010703:Phorbol Esters; D003907:Dexamethasone; D005934:Glucagon; D014444:Tyrosine Transaminase; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate