Regulation of steroid 21-hydroxylation by 17 beta-estradiol in rat liver: in vivo and in vitro study.
In various extraadrenal organs, progesterone (P4) is converted to deoxycorticosterone (DOC) by steroid 21-hydroxylation. To investigate the regulation of extraadrenal 21-hydroxylase activity by 17 beta-estradiol (E2), the following two experiments were performed. Exp. 1). Three-week-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), microsomal 21-Hydroxylase activity and the expression of P450c21 mRNA of the liver 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 production of DOC in the medium containing P4. The results of experiment 1 showed that both serum DOC concentration and 21-hydroxylase activity in the liver microsomal fraction were increased by E2 injection, but the 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 manner. These data provided evidence that: in rats the liver was one sites of the extraadrenal steroid 21-hydroxylase activity which had been stimulated by E2. The results also suggested that this hepatic enzyme was a different enzyme from the steroid 21-hydroxylase P450c21 expressed in the adrenal gland.
Department of Pediatrics, Hamamatsu University School of Medicine, Japan.
H
H
Natsume
A
A
Endoh
Y
Y
Nakagawa
Y
Y
Igarashi
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003900:Desoxycorticosterone / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009919:Orchiectomy; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*; D013268:Stimulation, Chemical
D012333:RNA, Messenger; D003900:Desoxycorticosterone; D011374:Progesterone; D004958:Estradiol; D013255:Steroid 21-Hydroxylase