Studies on Androgen Metabolism in Experimentally Feminized Rats

Abstract
Administration of the anti-androgen l,2α-methylene-6-chloropregna-4,6-diene-17α- ol-3,20-dione (cyproterone) to pregnant rats leads to feminization of the male offspring. Testicular tissue from these animals has been incubated with labeled pregnenolone, progesterone, dehydroepiandrosterone and androstenedione. The principal radiometabolites have been identified and compared with those obtained from the testes of healthy rats of the same age and strain. In addition, the metabolism of testosterone by scrotal skin from both groups of animals has been compared. Under these experimental conditions there was no consistent evidence for increased synthesis of estrone or estradiol-17β by testicular tissue from feminized animals. Testosterone was synthesized in good yield by both groups, but was significantly lower from progesterone (p 0.001; t test) and pregnenolone (p 0.001; t test) in testicular tissue from the feminized animals. This indirect analysis of enzymatic activity suggests decreased 17α-hydroxylation and side chain cleavage of Δ4-3-ketonic intermediaries in testicular tissue from feminized animals. However, with these testes there was a significantly higher yield of testosterone from dehydroepiandrosterone (p 0.001; t test) and androstenedione (p 0.001; t test). Scrotal skin from the feminized animals transformed testosterone to a spectrum of metabolites similar to that of the corresponding tissue from healthy males. There was a similar yield of androstenedione, but a significantly lower conversion to 5a-dihydrotestosterone (p 0.01-0.001; t test). (Endocrinology89: 553, 1971)