Antiandrogenic Effects of Oestradiol on Enzyme Activities of Hepatic Steroid Metabolism

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Abstract
Intact female rats and gonadectomized rats of both sexes were administered 0.5 mg 5α-dihydrotestosterone s.c. daily for 15 days. On the 16th day the activities of hepatic microsomal 3α and 3β-hydroxysteroid dehydrogenase and 5α-reductase were determined. Androgen. treatment increased the activity of both hydroxysteroid dehydrogenases and decreased the activity of the 5α-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 μg/day; 15 days s.c.) completely reversed the action of 5α-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).

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