Studies on the Inhibition of Fetal Androgen Formation: Testosterone Synthesis by Fetal and Newborn Mouse Testesin Vitro

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Abstract
The capacity of mouse testes to synthesize testosterone during fetal development, and the effects on synthesis of an inhibitor of 3- keto-4-steroid formation, 2α-cyano-4,4,17α-trimethyl- 17β-hydroxy-5-androsten-3-one (WIN) were studied. In fetal rats, WIN inhibited testicular 3 (3-hydroxy-5-steroid dehydrogenase activity and retarded development of the external genitalia (Goldman et al., Proc Soc Exp Biol Med121: 757, 1966). Testes of fetal (14.5 and 17.5 days of gestation) and newborn mice from untreated mothers converted 4-14C-pregnenolone to 14C-testosterone during in vitro incubations. The results demonstrated testicular capacity for steroid metabolism to testosterone during the period of reproductive tract differentiation in mice. WIN, injected at doses of 1.5–7.0 mg/kg body weight into 12.5–15.5 day pregnant mice, exerted no effects on the gross development of the structures of the reproductive tract in either sex or on the conversion of 4-14C-pregnenolone to testosterone by fetal or newborn testes. Fetal resorption occurred at higher concentrations. Since rats are able to tolerate a minimally 15-fold larger dose of WIN without interfering with continued maintainance of pregnancy, a species difference seems to exist in this action of WIN. Administration to pregnant mice of 3-(6-chloro-3-methyl-2-indenyl) pyridine, an inhibitor of 17α-hydroxylase activity, failed to influence development of the reproductive tracts. In additional experiments, 4-14C-pregnenolone, 4-14C-progesterone and 7α- 3H-17α-hydroxypregnenolone were found to be efficient, potential precursors for testosterone synthesis by neonatal mouse testes. (Endocrinology88: 41, 1971)

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