Sex Hormone Biosynthesis

The sex Hormone Biosynthetic pathway (also called Steroidogenesis) is an enzymatic cascade by which cholesterol is converted to biologically active steroid hormones. The first (rate-limiting) enzymatic step consists in the conversion of cholesterol into pregnenolone by P450 side chain cleavage (CYP11A1). Pregnenolone can subsequently be converted into progesterone by 3-beta-hydroxysteroid dehydrogenase (HSD3B1 and HSD3B2) or into 17-hydroxypregnenolone by 17-alpha-hydroxylase/17,20 lyase (CYP17A1). Then, CYP17A1 can convert progesterone into 17-hydroxyprogesterone, whereas HSD3B1 can convert 17-hydroxypregnenolone into 17-hydroxyprogesterone. In a next step, 17-hydroxypregnenolone and 17-hydroxyprogesterone can be converted by CYP17A1 into dehydroepiandrosterone (DHEA) and androstenedione, respectively. In turn, the activity of different 17beta-HSD enzymes catalyzes the synthesis of androstenediol from DHEA and testosterone from androstenedione. Aromatase converts androstenedione and testosterone into estrone and beta-estradiol, respectively. Considering glucocorticoids, the synthesis of 11-deoxycortisol and 11-deoxycorticosterone from 17-hydroxyprogesterone and progesterone, respectively, are catalyzed by 21-hydroxylase (CYP21A2), followed by the P450C11 (CYP11B1 and CYP11B2) activity leading to the synthesis of cortisol and corticosterone.