REGULATION OF STEROID 21-HYDROXYLATION BY 17-BETA-ESTRADIOL IN RAT-LIVER - INVIVO AND INVITRO STUDY

In various extraadrenal organs, progesterone (P4) is converted to deox ycorticosterone (DOC) by steroid 21-hydroxylation. To investigate the regulation of extraadrenal 21-hydroxylase activity by 17beta-estradiol (E2), the following two experiments were performed. Exp. 1). Three-we ek-old male SD rats were testectomized (TX) and injected with E2 (1 mg ) or sesame-oil s.c. Sham rats were treated with sesame-oil. In these groups the serum concentration of DOC and corticosterone (B), microsom al 21-Hydroxylase activity and the expression of P450c21 mRNA of the l iver and the adrenals were analyzed. Exp. 2). Isolated rat hepatocytes were cultured and stimulated by E2, 10(-9) approximately 10(-5) M. 21 -Hydroxylase activity of these cells was analysed by the rate of produ ction of DOC in the medium containing P4. The results of experiment 1 showed that both serum DOC concentration and 21-hydroxylase activity i n the liver microsomal fraction were increased by E2 injection, but th e expression of P450c21 mRNA was not detected in the liver even after E2 injection. In experiment 2, the activity of steroid 21-hydroxylase in isolated rat hepatocytes was stimulated by E2 in a dose dependent m anner. These data provided evidence that: in rats the liver was one si tes of the extraadrenal steroid 2 1 -hydroxylase activity which had be en stimulated by E2. The results also suggested that this hepatic enzy me was a different enzyme from the steroid 21-hydroxylase P450c21 expr essed in the adrenal gland.