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Rat Fetal Target Organ ⁵5,3β–Hydroxysteroid Dehydrogenase: Effect of Cyanoketone and Cyproterone Acetate

Division of Experimental Pathology, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania

Abstract

The metabolism of dehydroepiandrosterone–7a–3H and testosterone–1,2–³H by the wolffian duct and genital skin of term rat male fetuses treated in utero with cyanoketone, cyproterone acetate or vehicle has been studied by a micro-method permitting enzymatic analysis on as little as 1 mg of tissue. The metabolic products have been quantitated by a novel partition system on thin—layer chromatography which separates most of the androgen metabolites formed from these substrates by these rat tissues.

The present report demonstrates, both in the duct and in the genital skin of term fetuses, the presence of an active 5,3β–hydroxysteroid dehydrogenase capable of transforming dehydroepiandrosterone to androstenedione, testosterone, and 5––reduced metabolites. Cyanoketone inhibits the dehydrogenase both in the ducts and genital skin. In vivo administration but not in vitro inclusion of cyproterone—acetate and cyanoketone significantly reduces the conversion of testosterone–1,2–³H by term male genital skin to 5–reduced metabolites.Genital skin of adult females and of adult males "feminized" by in utero and postnatal treatment with cyproterone—acetate have been reported to convert less testosterone to 5–reduced metabolites than that of adult males. The present observations suggest that this "feminization" is also produced by cyanoketone and is present at birth. (Endocrinology 92: 1043, 1973)

Footnotes

¹ Recipient of Career Development Award (HD–13,628) from the USPHS.

Received August 28, 1972.