Molecular Genetics, Structure-Function Relationships, and Tissue-Specific Expression and Regulation of the 3βHSD Gene Family

Abstract

Despite its essential role in the biosynthesis of all classes of hormonal steroids, structure of the 3β-hydroxysteroid dehydrogenase/ Δ 5 - Δ 4 -isomerase (3βHSD) gene family was only recently elucidated (1). This enzyme, as illustrated in Figure 7.1, is required for the biosynthesis of progesterone, glucocorticoids, and mineralocorticoids, as well as androgens and estrogens. 3βHSD is found not only in classical steroidogenic tissues—namely, the placenta, adrenal cortex, ovary, and testis—but also in several peripheral tissues, including the skin, adipose tissue, breast, lung, endometrium, prostate, liver, kidney, epididymis, and brain (1). The widespread distribution of 3βHSD expression indicates that this enzyme is likely to play an important role in the intracrine (2) formation of sex steroids in peripheral target tissues. Such a high level of extragonadal formation of sex steroids is especially important in the human and some other primates whose adrenals secrete large amounts of the precursor sex steroids dehydroepiandrosterone (DHEA) and especially DHEA sulfate (2–5).