Human 17βHSD type 2 reversibly interconverts androgens and estrogens at equal rates in vivo

Abstract

Objective: The 17β-hydroxysteroid dehydrogenase enzymes (17βHSDs) are responsible for interconversion between the hydroxy- and ketosteroid pairs using the cofactors NAD(P)H/NAD(P)+. Thus, the 17βHSDs complete biosynthetic pathways to active hormones and regulate the intracellular concentrations of active and inactive forms of steroids. In vitro, these enzymes drive the reaction in either oxidative or reductive directions, depending on the pH and cofactors. However, in vivo, these enzymes appear to function unidirectionally, either as a reductase or as an oxidative dehydrogenase. When studied in transfected HEK-293 cells, 17βHSD type 2 converts estradiol (E2) almost completely to estrone (E1) but appears not to convert E2 to E1, suggesting that the 17βHSD type 2 functions exclusively as a steroid dehydrogenase in living cells. Likewise, 17βHSD type 2 also converts testosterone (T) almost completely to androstenedione (AD) without measurable activity in the reverse direction. Conversely, 17βHSDs types 1 and 3 principally reduce E1 to E2 and AD to T, respectively.