Steroid 5α-reductase 1 promotes 5α-androstane-3α,17β-diol synthesis in immature mouse testes by two pathways

Abstract

5α-Androstane-3α,17β-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5α-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24–26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone → dihydrotestosterone → androstanediol, and a second utilizes the pathway progesterone → 5α-dihydroprogesterone → 5α-pregnane-3α-ol-20-one → 5α-pregnane-3α,17α-diol-20-one → androsterone → androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5α-reductase 2 but absent in testes from mice deficient in steroid 5α-reductase 1, indicating that isoenzyme 2 is not expressed in day 24–26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [ 3 H ]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.