The regulation of 3β-hydroxysteroid dehydrogenase expression

3β-Hydroxysteroid dehydrogenase/Δ(5→4)-isomerase (3β-HSD) catalyzes the formation of Δ⁴-3-ketosteroids from Δ⁵-3β-hydroxysteroids, an obligate step in the biosynthesis not only of androgens and estrogens but also of mineralocorticoids and glucocorticoids. The enzyme is expressed in the adrenal cortex and in steroidogenic cells of the gonads, consistent with this role. However, 3β-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 a family of closely related genes encode for 3β-HSD. The various 3β-HSD isoforms are expressed in a tissue-specific manner involving separate mechanisms of regulation. The human type 1 3β-HSD is expressed at high levels in syncytial trophoblast and in sebaceous glands, and the type II isoform is almost exclusively expressed in the adrenal cortex and gonads. An important feature in liver and kidney (at least of hamster, mouse, rabbit, and rat) is the sexual dimorphic nature of 3β-HSD expression. We briefly review studies on the regulation of the human 3β-HSD I and II genes in human trophoblast and adrenal cortex and extend this to discuss the rat 3β-HSD I gene expressed in adrenals and gonads. The complexity of 3β-HSD expression through multiple signaling pathways acting on a multigene family of enzymes may contribute importantly to the diverse patterns and locations of steroid hormone biosynthesis.