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
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
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DOI：
10.1210/endo-113-3-1043
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发表时间：
1983-01-01
期刊：
影响因子：
4.8
通讯作者：
SCHRIEFERS, H
中科院分区：
文献类型：
--
作者：
LAX, ER;RUMSTADT, F;SCHRIEFERS, H
每日雌激素（雌二醇、乙炔雌二醇、己烯雌酚）给药对3种肝雄激素依赖性微粒体酶（3 α-β-D）活性的剂量依赖性作用3. beta.-羟基类固醇脱氢酶和5 α-还原酶）。然后测试抗雌激素阻断10 μ g雌二醇/天对这些酶活性的女性化作用的能力;萘福昔定和单羟基他莫昔芬最有效。预防5. alpha.-研究了去卵巢雌性动物中二氢睾酮诱导的这些活性的变化。所有3种雌激素在1 μ g剂量下均阻断500 μ g雄激素的作用。通过每天给予5 mg氟替卡松或恒定输注人GH [生长激素]（5 μ g/h）实现类似的雄激素阻断。同时给予200 μ g单羟基他莫昔芬阻止雌激素的雄激素拮抗作用，但不能阻止氟替卡松或GH的雄激素拮抗作用。大剂量的雌激素对5 α-雌二醇具有与雄激素相同的抑制作用。还原酶活性。使用己烯雌酚处理的大鼠作为模型，它表明，这种影响可以通过抗雌激素，但不能通过GH。雄激素和低剂量的雌激素通过作用于不同水平的中枢调节来影响这些酶的活性，而大剂量的雌激素通过肝雌激素受体直接作用于肝脏。肝雌激素受体浓度的研究证实了这些结论。
The dose-dependent effects of daily estrogen (estradiol, ethinyl estradiol, diethylstilbestrol) administration on the activities of 3 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 .mu.g 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 3 estrogens at a dose of 1 .mu.g blocked the action of 500 .mu.g androgen. A similar androgenic blockade was achieved by daily administration of 5 mg flutamide or constant infusion of human GH [growth hormone] (5 .mu.g/h). Simultaneous administration of 200 .mu.g 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. Androgens and low doses of estrogens affect these enzyme activities by acting at different levels of central regulation, while large doses of estrogens act directly on the liver via hepatic estrogen receptors. These conclusions are corroborated by studies of hepatic estrogen receptor concentrations.