Effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) on the enzymes of phase I (CYP2B1/2) and phase II (SULT1A and COMT) metabolism, and differences in the action of parent BDE-47 and its hydroxylated metabolites, 5-OH-BDE-47 and 6-OH-BDE47, on steroid secretion by luteal cells

Abstract

In this study we determined the effects of BDE-47 on the expression and activity of phase I (CYP2B1/2) and phase II (SULT1A and COMT) enzymes, and assessed the actions of BDE-47 and its metabolites on luteal steroidogenesis. Luteal cells collected during early (ELP), middle (MLP) and late (LLP) luteal phase were exposed to BDE-47 (0.5, 25, and 50ng/ml) or metabolites (2.5, 5 and 25ng/ml). BDE-47 decreased CYP2B1/2 activity and expression but had no effect on SULT1A or COMT. BDE-47 exerted a stimulatory action on estrogen secretion in MLP and an inhibitory in LLP, but had no effect on progesterone secretion. 5-OH-BDE-47 and 6-OH-BDE-47 decreased progesterone, but had no effect on estrogen secretion. ConclusionsThe inhibitory effect of BDE-47 on CYP2B1/2 suggests the possibility of BDE-47 accumulation in the corpus luteum; by affecting steroid secretion and steroidogenesis enzymes, BDE-47 and its metabolites can be responsible for shortening luteal phase.