Time-Studies of the Changes in the Sex-Dependent Activities of Enzymes of Hepatic Steroid Metabolism in the Rat during Oestrogen Administration

Abstract

This investigation was undertaken to elucidate the amount of estradiol and duration of its administration necessary to cause complete feminization of the activities of cytoplasmic 3.alpha.- and 17.beta.-hydroxysteroid dehydrogenase, microsomal 3.alpha.- and 3.beta.-hydroxysteroid dehydrogenase and microsomal 5.alpha.-reductase in male rat liver. With the exception of cytoplasmic 3.alpha.-hydroxysteroid dehydrogenase, 5 .mu.g estradiol/day for 8 days and less was sufficient to cause complete feminization. The order of estrogen sensitivity was cytoplasmic 3.alpha.-hydroxysteroid dehydrogenase .mchgt. microsomal 3.beta.-hydroxysteroid dehydrogenase > microsomal 3.alpha.-hydroxysteroid dehydrogenase > microsomal 5.alpha.-reductase > cytoplasmic 17.beta.-hydroxysteroid dehydrogenase. Although the changes occurring after estradiol administration are qualitatively the same as after testectomy, they occur more rapidly. This rules out the possibility that estradiol exerts its effect via androgen deprivation. Diethylstilbestrol administration causes the same changes in cytoplasmic 17.beta.- and microsomal 3.beta.-hydroxysteroid dehydrogenase activity as estradiol, although the dosage must be increased 100-fold. The effect of diethylstilbestrol on 5.alpha.-reductase activity changes with the dose applied. Doses up to 100 .mu.g/day partially feminize the activity, but at higher doses the enzyme activity is repressed.