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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^*

E. R. LAX, F. RUMSTADT, H. PLASCZYK, A. PEETZ and H. SCHRIEFERS

Institut fur Physiologische Chemie, Universitdtsklinikum-Essen, Hufelandstrafie 55 D-4300 Essen, Federal Republic of Germany

Abstract

The dose-dependent effects of daily estrogen (estradiol, ethinyl estradiol, diethylstilbestrol) administration on the activities of three hepatic androgen-dependent microsomal enzymes (3- and 3β-hydroxysteroid dehydrogenase and 5reductase) in male rats were examined. Antiestrogens were then tested for their ability to block the feminizing action of 10 µg estradiol/day on these enzyme activities; nafoxidine and monohydroxytamoxifen were the most effective. The prevention of 5-dihydrotestosterone-induced changes in these activities in ovariectomized females was investigated. All three estrogens at a dose of 1 µg blocked the action of 500 µg androgen. A similar androgenic blockade was achieved by daily administration of 5 µg flutamide or constant infusion of human GH (5 µg/h). Simultaneous administration of 200 µg 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-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. (Endocrinology 113: 1043,1983)

Footnotes

^* This project was supported by Landesamt fur Forschung des Landes Nordrhein-Westfalen Grant IV B 5-FA 6897 (enzyme activity determinations) and Deutsche Forschungsgemeinschaft Grant La 459/1–1 (HASP binding determination).

To whom correspondence and requests for reprints should be sent.

Received December 22, 1982.

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