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

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 w...

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Bibliographic Details
Published in:	Endocrinology (Philadelphia) Vol. 113; no. 3; p. 1043
Main Authors:	Lax, E R, Rumstadt, F, Plasczyk, H, Peetz, A, Schriefers, H
Format:	Journal Article
Language:	English
Published:	United States 01-09-1983
Subjects:	3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) 3-Hydroxysteroid Dehydrogenases - metabolism 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism Androgen Antagonists Anilides - pharmacology Animals Castration Estrogen Antagonists - pharmacology Estrogens - pharmacology Female Flutamide - pharmacology Growth Hormone - pharmacology Male Microsomes, Liver - enzymology Nafoxidine - pharmacology Rats Rats, Inbred Strains Steroids - metabolism Tamoxifen - analogs & derivatives Tamoxifen - pharmacology
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Summary:	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.
ISSN:	0013-7227
DOI:	10.1210/endo-113-3-1043