Antiandrogenic effects of oestradiol on enzyme activities of hepatic steroid metabolism.
Intact female rats and gonadectomized rats of both sexes were administered 0.5 mg 5 alpha-dihydrotestosterone s.c. daily for 15 days. On the 16th day the activities of hepatic microsomal 3 alpha- and 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase were determined. Androgen treatment increased the activity of both hydroxysteroid dehydrogenases and decreased the activity of the 5 alpha-reductase in all animal models. Simultaneous administration of a steroidal antiandrogen, cyproterone (5 mg/day; 15 days s.c.) did not prevent this androgenic effect, whereas oestradiol (5 micrograms/day; 15 days s.c.) completely reversed the action of 5 alpha-dihydrotestosterone. The nonsteroidal antiandrogen, flutamide, also exhibited a potent antiandrogenic influence on these enzyme activities in female rats, whereas its antagonizing action in males was limited. The effects of cyproterone, oestradiol and flutamide on enzyme activities of hepatic steroid metabolism do not reflect the biological activity of these compounds on the weights of target organs (uterus, seminal vesicle, levator ani).
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D002369:Castration; D003534:Cyproterone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D013196:Dihydrotestosterone; D004958:Estradiol; D005485:Flutamide; D003534:Cyproterone; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase