DUAL REGULATION OF 21-HYDROXYLASE ACTIVITY BY SEX STEROID-HORMONES INRAT HEPATOCYTES

In the rat liver, cytochrome P450 catalyzes the hydroxylation of stero id hormones. The expression and activity of some P450 isozymes are reg ulated by sex steroid hormones. Steroid 21-hydroxylase activity in rat liver is provided mainly by CYP2C6. We studied the regulation of 21-h ydroxylase activity by sex steroid hormones in rat primary hepatocyte culture. We added estrogens (estrone, estradiol, estriol) and androgen s (testosterone, dihydrotestosterone), ranging from 10(-9) to 10(-5) M ) to the culture. The 21-hydroxlyase activity was stimulated by estrog ens and was suppressed slightly by androgen in a dose-related manner. The results of our studies demonstrated that sex steroid hormones act differently on 21-hydroxylase activity in rat hepatocytes and, thus, s upport the hypothesis that the extra-adrenal production of deoxycortic osterone from circulating progesterone is increased during pregnancy b y the massive presence of estrogens.