Endocrine disruptors of inhibiting testicular 3β-hydroxysteroid dehydrogenase

Abstract

Testicular 3β-hydroxysteroid dehydrogenase (HSD3B) is a steroidogenic enzyme, catalyzing the conversion of 3β-hydroxysteroids into 3-keto-steroids. Two distinct isoforms in the human are cloned, HSD3B1 and HSD3B2, and HSD3B2 is located in the testis. HSD3B2 is a two-substrate enzyme, which binds to cofactor NAD⁺ and a 3β-steroid. Many endocrine disruptors, including industrial compounds (phthalates, bisphenols, and perfluoroalkyl substances), insecticides and biocides (organochlorine insecticides and organotins), food additives (butylated hydroxyanisole, resveratrol, gossypol, flavones, and isoflavones), and drugs (etomidate, troglitazone, medroxyprogesterone acetate, and ketoconazole) inhibit testicular HSD3B, possibly interfering with androgen synthesis. In this review, we discuss the distinct testicular isoform of HSD3B, its gene, chemistry, subcellular location, and the endocrine disruptors that directly inhibit testicular HSD3B and their inhibitory modes.

Keywords: 3β-hydroxysteroid dehydrogenase; Environmental endocrine disruptors; Phthalates; Polyphenols; Steroidogenesis; Testosterone production.