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Endocrinology, Vol 113, 1043-1055, Copyright © 1983 by Endocrine Society

ARTICLES

Antagonistic action of estrogens, flutamide, and human growth hormone on androgen-induced changes in the activities of some enzymes of hepatic steroid metabolism in the rat

ER Lax, F Rumstadt, H Plasczyk, A Peetz and H Schriefers

The dose-dependent effects of daily estrogen (estradiol, ethinyl estradiol, diethylstilbestrol) administration on the activities of three hepatic androgen-dependent microsomal enzymes (3 alpha- and 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase) in male rats were examined. Antiestrogens were then tested for their ability to block the feminizing action of 10 micrograms estradiol/day on these enzyme activities; nafoxidine and monohydroxytamoxifen were the most effective. The prevention of 5 alpha-dihydrotestosterone-induced changes in these activities in ovariectomized females was investigated. All three estrogens at a dose of 1 microgram blocked the action of 500 micrograms androgen. A similar androgenic blockade was achieved by daily administration of 5 mg flutamide or constant infusion of human GH (5 micrograms/h). Simultaneous administration of 200 micrograms monohydroxytamoxifen prevented the androgen-antagonizing action of estrogens, but not of flutamide nor of GH. Large doses of estrogens have the same repressive effect as androgens on 5 alpha-reductase activity in female castrates. Using the diethylstilbestrol-treated rat as a model, it is demonstrated that this effect can be prevented by antiestrogen, but not by GH. It is concluded that androgens and low doses of estrogens affect these enzyme activities by acting at different levels of central regulation, whereas large doses of estrogens act directly on the liver via hepatic estrogen receptors. These conclusions are corroborated by studies of hepatic estrogen receptor concentrations.


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S. M. Hyder, C. Chiappetta, and G. M. Stancel
Synthetic Estrogen 17alpha -Ethinyl Estradiol Induces Pattern of Uterine Gene Expression Similar to Endogenous Estrogen 17beta -Estradiol
J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 740 - 747.
[Abstract] [Full Text]


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Copyright © 1983 by The Endocrine Society