THE REGULATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE EXPRESSION

3 beta-Hydroxysteroid dehydrogenase/Delta(5-->4)-isomerase (3 beta-HSD ) catalyzes the formation of Delta(4)-3-ketosteroids from Delta(5)-3 b eta-hydroxysteroids, an obligate step in the biosynthesis not only of androgens and estrogens but also of mineralocorticoids and glucocortic oids. The enzyme is expressed in the adrenal cortex and in steroidogen ic cells of the gonads, consistent with this role. However, 3 beta-HSD is also expressed in many other tissues, such as the liver and kidney , where its function is not entirely clear. It is established that fam ily of closely related genes encode for 3 beta-HSD. The various 3 beta -HSD isoforms are expressed in a tissue-specific manner involving sepa rate mechanisms of regulation. The human type I 3 beta-HSD is expresse d at high levels in syncytial trophoblast and in sebaceous glands, and the type II isoform is almost exclusively expressed in the adrenal co rtex and gonads. An important feature in liver and kidney (at least of hamster, mouse, rabbit, and rat) is the sexual dimorphic nature of 3 beta-HSD expression. We briefly review studies on the regulation of th e human 3 beta-HSD I and II genes in human trophoblast and adrenal cor tex and extend this to discuss the rat 3 beta-HSD I gene expressed in adrenals and gonads. The complexity of 3 beta-HSD expression through m ultiple signaling pathways acting on a multigene family of enzymes may contribute importantly to the diverse patterns and locations of stero id hormone biosynthesis. (C) 1997 by Elsevier Science Inc.