Molecular Biology of Steroid Hormone Synthesis*

STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocorticoids, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which are essential for reproduction; and androgens, which induce male secondary sexual characteristics. These classes of steroid hormones are structurally similar and arise from a common series of pathways. They are distinguished by their actions on one or more specific steroid hormone receptors. The hormone/receptor complexes function as tissue-specific transcriptional regulators of distinct domains of genes and, consequently, exert their broad array of physiological effects. (For reviews, see Refs. 1 and 2.) The pathways by which these steroid hormones are produced from cholesterol were initially studied by studying the structures of the steroids themselves. Over the past 30 yr, studies of enzyme kinetics and of steroidal precursorproduct relationships have led to the widely held belief that a very large number of distinct enzymes are involved in the conversion of cholesterol and its esters to active steroid hormones. The application of modern protein chemistry and molecular biology to these questions has radically changed this view.