alexa Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Steroids & Hormonal Science

Author(s): Kojima H, Takeuchi S, Uramaru N, Sugihara K, Yoshida T,

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Abstract BACKGROUND: An increasing number of studies are reporting the existence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (HO) and methoxylated (MeO) metabolites in the environment and in tissues from wildlife and humans. OBJECTIVE: Our aim was to characterize and compare the agonistic and antagonistic activities of principle PBDE congeners and their HO and MeO metabolites against human nuclear hormone receptors. METHODS: We tested the hormone receptor activities of estrogen receptor alpha (ERalpha), ERbeta, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor alpha(1) (TRalpha(1)), and TRbeta(1) against PBDE congeners BDEs 15, 28, 47, 85, 99, 100, 153, and 209, four para-HO-PBDEs, and four para-MeO-PBDEs by highly sensitive reporter gene assays using Chinese hamster ovary cells. RESULTS: Of the 16 compounds tested, 6 and 2 showed agonistic activities in the ERalpha and ERbeta assays, respectively, and 6 and 6 showed antagonistic activities in these assays. 4'-HO-BDE-17 showed the most potent estrogenic activity via ERalpha/beta, and 4'-HO-BDE-49 showed the most potent anti estrogenic activity via ERalpha/beta. In the AR assay, 13 compounds showed antagonistic activity, with 4'-HO-BDE-17 in particular inhibiting AR-mediated transcriptional activity at low concentrations in the order of 10(-8) M. In the GR assay, seven compounds, including two HO-PBDEs and two MeO-PBDEs, showed weak antagonistic activity. In the TRalpha(1) and TRbeta(1) assays, only 4-HO-BDE-90 showed weak antagonistic activity. CONCLUSIONS: Taken together, these results suggest that PBDEs and their metabolites might have multiple endocrine-disrupting effects via nuclear hormone receptors, and para-HO-PBDEs, in particular, possess more potent receptor activities compared with those of the parent PBDEs and corresponding para-MeO-PBDEs.
This article was published in Environ Health Perspect and referenced in Journal of Steroids & Hormonal Science

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