GLUCOCORTICOID INDUCTION OF HEPATIC ACETYL COA-ARYLAMINE N-ACETYLTRANSFERASE ACTIVITY IN THE RAT

N-Acetylation, which is catalyzed by the enzymes N-acetyltransferase ( NAT), is an important biotransformation pathway for the elimination of a wide variety of xenobiotics. Based on reports by several investigat ors that hydrocortisone (HYD) pretreatment increases N-acetylation in the rabbit, we examined the potential of glucocorticoids to induce NAT in the rat. Rats received pretreatment with relatively equipotent dos es of HYD, prednisolone (PRED) or dexamethasone (DEX) for 5 or 10 days . Livers were removed 24 hr after the last dose and NAT activity was d etermined by measuring the formation of N-acetylprocainamide in cytoso lic incubations in the presence of 0.42 mM acetyl CoA. All three gluco corticoids were found to cause a modest induction of NAT activity towa rds procainamide after dosing for 10 days. When normalized to cytosoli c protein content, the potency. of induction was PRED > DEX > HYD (30, 29 and 18% increase, respectively), while normalization to liver weig ht demonstrated equipotent NAT induction by the three agents (40%). Th ese data indicate that glucocorticoids are capable of producing a mode st induction of NAT activity in the rat.