Inhibitors of Corticosteroid Synthesis

Corticosteroids, chiefly cortisol and aldosterone, are synthesized from cholesterol by way of pregnenolone utilizing a number of cytochrome P450 enzymes, which can be inhibited by several drugs. Because sex hormone synthesis shares common pathways with corticosteroids, the synthesis of gonadal and placental steroids may also be inhibited. These drugs include mitotane, aminoglutethimide (inhibits cholesterol side-chain cleavage enzyme), metyrapone, (inhibits steroid 11beta-hydroxylase), and trilostane (inhibits 3beta-hydroxysteroid dehydrogenase). Ketoconazole also potently inhibits steroid biosynthesis by blocking steroid 11beta-hydroxylase and 17alpha-hydroxylase, which catalyzes the conversion of 17alpha-hydroxyprogesterone to androstenedione. Etomidate, an anesthetic agent, is an inhibitor of 11beta-hydroxylase.