Environmental pollutants and hydroxysteroid dehydrogenases

Hydroxysteroid dehydrogenases (HSD) are a group of steroidogenic enzymes that are involved in the steroid biosynthesis and metabolism. Four classes of HSDs, namely, 3β-, 11β-, 17β-, and 20α-HSDs, are discussed. 3β-HSDs catalyze the conversion of pregnenolone, 17α-hydroxypregnenolone, and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone, and androstenedione, respectively. 11β-HSDs catalyze the interconversion between active cortisol and inactive cortisone. 17β-HSDs catalyze the interconversion between 17β-hydroxyl steroids and 17-ketoandrogens and estrogens. 20α-HSDs catalyze the conversion of progesterone into 20α-hydroxyprogesterone. Many environmental pollutants directly inhibit one or more enzymes of these HSDs, thus interfering with endogenous active steroid hormone levels. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A, and benzophenone), pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane, and prochloraz), and plant constituents (genistein, gossypol, and licorice). This chapter reviews these inhibitors targeting on HSDs.