Leydig cell androgen synthesis

Testosterone and its metabolite dihydrotestosterone (DHT) are the main androgens driving male sexual differentiation and masculinization, and supporting spermatogenesis. They are synthesized by the Leydig cells of the testis from cholesterol transferred from intracellular stores into mitochondria; the hormone-sensitive and rate-limiting step in androgen biosynthesis. In mitochondria, cholesterol is metabolized by the cytochrome CYP11A1 into pregnenolone, which is further metabolized to androgens in the endoplasmic reticulum by the 3β-HSD, CYP17A1, and 17β-HSD3 enzymes. Testosterone is metabolized to estradiol and DHT by CYP19A1 and 5α-reductase, respectively. Deficiencies in androgen biosynthesis are relatively rare and lead to male pseudohermaphroditism.