描述
Steroidogenesis is the process wherein desired forms of steroids are generated by transformation of other steroids. Products of steroidogenesis include androgens, testosterone, estrogens and progesterone, corticoids, cortisol and aldosterone. The first step in the synthesis of all steroid hormones is the synthesis of pregnenolone from cholesterol. In this process, cholesterol mobilized from cytosolic lipid droplets or from lysosomes is transported to mitochondria and becomes localized to the inner mitochondrial membrane. In the inner mitochondrial membrane, cholesterol is converted to pregnenolone in a sequence of three reactions, all catalyzed by CYP11A (side chain cleavage enzyme). Finally, pregnenolone re-enters the cytosol. Pregnenolone is converted to progesterone in two reactions, both catalyzed by 3-beta-hydroxysteroid dehydrogenase/isomerase. Progesterone is hydroxylated by CYP21A2 to form deoxycorticosterone, which in turn is converted to aldosterone in a three-reaction sequence catalyzed by CYP11B2. Pregnenolone is converted to 17alpha-hydoxyprogesterone in two reactions, both catalyzed by 3-beta-hydroxysteroid dehydrogenase/isomerase. 17Alpha-hydroxyprogesterone is hydroxylated by CYP21A2 to form 11-deoxycortisol, which in turn is converted to cortisol by CYP11B1. The conversion of the active steroid hormone, cortisol, to inactive cortisone occurs in many tissues, notably the liver. Testosterone biosynthesis begins with pregnenolone. Subsequent steps require several enzymes including, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/C17-20-lyase and 17β-hydroxysteroid dehydrogenase type 3. Specifically, pregnenolone is converted to 17-hydroxypregnenolone and dehydroepiandrosterone by CYP17 (17α-hydroxylase). Dehydroepiandrosterone is then converted to androstenedione by 3β-hydroxysteroid dehydrogenase. Androstenedione can have two fates, it can either be converted to estrone via CYP19 (aromatase/estrogen synthase) or it can be converted to testosterone via 17β-hydroxysteroid dehydrogenase. Free testosterone is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. Testosterone may also be converted to estradiol by the action of CYP19 (aromatase/estrogen synthase).