Different action of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and its hydroxylated metabolites on ERα and ERβ gene and protein expression

Abstract

In our previously published data we showed that PBDEs act as endocrine disruptors in ovarian follicles by altering steroid secretion.In this study we try to answer a question if BDE-47 and its hydroxylated metabolites (5-OH-BDE-47 and 6-OH-BDE-47) can act as endocrine disruptors in the ovary by changing the expression of the steroid nuclear receptors, estrogen receptor alpha (ERα) and beta (ERβ), androgen receptor (AR), and receptors associated with the metabolism of xenobiotics and steroid hormones, constitutive androstane receptor (CAR) and pregnane X-receptor (PXR), in porcine ovarian follicles. Expression of mRNA was evaluated by real-time PCR, whereas protein level by western blotting.CAR and PXR mRNAs were not expressed in porcine ovarian follicular cells. BDE-47 and its hydroxylated metabolites had no effect on the expression of AR mRNA and protein. Decreased expression of ERβ mRNA and protein under BDE-47 influence and increase both ERα and ERβ gene and protein expression in cells exposed to hydroxylated metabolites was noted. These findings indicate that BDE-47, by altering the ratio of ERα to ERβ toward ERα, and the hydroxylated metabolites of BDE-47, by increase estrogen receptors expression, may result in excessive ovarian exposure to estrogens.