Studies of the Human Testis. III. Effect of Estrogen on Testosterone Formation in Human Testisin Vitro

Abstract

The effect of estradiol-17β on the conversion of ³H-dehydroepiandrosterone (DHA) in human testicular tissue was studied in 24-hr organ culture. With the addition of increasing amounts of estradiol-17β, the formation of radioactive testosterone was progressively reduced with parallel accumulation of labeled androst-5-ene-3β, 17β-diol (Δ⁵-diol). No change was observed in the recovery of labeled androst-4-ene-3,17-dione (Δ⁴-dione). When equal amounts of ³H-Δ⁵-diol and ¹⁴C-Δ⁴-dione were used as precursors, added estradiol-17β inhibited the conversion of Δ⁵-diol to testosterone but not the conversion of Δ⁴-dione to testosterone. Addition of testosterone to the organ culture inhibited the production of ³H-testosterone from ³H-DHA, while ³H-Δ⁵-diol increased with no change in ³H-Δ⁴-dione. Addition of Δ⁵-diol to the culture medium reduced formation of radioactive testosterone, Δ⁵-diol and Δ¹-dione from ³H-DHA. From these results it is concluded that estradiol-17β added in vitro has an inhibitory effect on 3β-hydroxysteroid dehydrogenase plus isomerase activity which is necessary for the conversion of Δ⁵-diol to testosterone in the biosynthetic pathway leading to testosterone from DHA. No in hibitory effect was observed on the activity of 17β-hydroxysteroid dehydrogenase.