Abstract
The development of mammary glands has been studied in fetuses of pregnant rats treated with an analog (2α-cyano-4, 4,17α-trimethyl-androst-5-en-17β3-ol-3-one) of a C-19 substrate of 3β-hydroxysteroid dehydrogenase and Δ5-4, 3-ketosteroid isomerase, which is a selective inhibitor of these enzymes. In male fetuses, the analog causes the development of nipples, which are normally suppressed by fetal testicular function. In light of the previous demonstration of the feminizing effect of the analog on the male external genitalia due to inhibition of the fetal testicular dehydrogenase, this observation suggests that inactivation of the testicular dehydrogenase system leads to insufficient endogenous Δ4,3-ketoandrogen (testosterone) production, thus allowing the development of the nipple in the male. In female fetuses, the analog inhibits nipple development, probably because of adrenal overproduction of 3β-hydroxyandrogens in response to inhibition of the adrenal dehydrogenase system.
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