Ovarian and Adrenal Androgen Biosynthesis and Metabolism

The pathways of adrenal and ovarian steroid biosynthesis use the same enzymes for the initial steps of steroidogenesis but express different enzymes that convert steroid precursors to the final active products. Both the adrenal and ovary produce dehydroepiandrosterone (DHEA), the principal precursor of androgens and estrogens. The key enzyme in DHEA production is P450c17, which catalyzes both 17α-hydroxylation and 17,20lyase activities. The 17,20-lyase activity of human P450c17 strongly favors 17-hydroxypregnenolone rather than 17-hydroxyprogesterone (17-OHP) as a substrate, producing abundant DHEA, so that most human androgens and estrogens derive from DHEA. Understanding the biochemistry of P450c17 is central to understanding the hyperandrogenism of polycystic ovary syndrome (PCOS). Rare genetic disorders of steroidogenesis provide human genetic knockout experiments of nature, yielding important information about the biosynthesis and physiological roles of steroids.