Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells.
Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells.
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DOI：
10.1289/ehp.0900753
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发表时间：
2009-08
影响因子：
10.4
通讯作者：
Kitamura S
中科院分区：
文献类型：
--
作者：
Kojima H;Takeuchi S;Uramaru N;Sugihara K;Yoshida T;Kitamura S
越来越多的研究报告称，环境中以及野生动物和人类的组织中存在多溴二苯醚(PBDEs)及其羟化(HO)和甲氧基化(MeO)代谢物。我们的目的是表征和比较主要的多溴二苯醚同系物及其HO和MeO代谢物对人核激素受体的激动性和拮抗性。以中国仓鼠卵巢细胞为材料，采用高灵敏度的报告基因分析方法，检测了雌激素受体α(ER-α)、ER-β、雄激素受体(AR)、糖皮质激素受体(GR)、甲状腺激素受体α-1(TR-α1)和TR-β1对BDE15、28、47、85、99、100、153和209、4个类HO-PBDEs和4个类MeO-PBDEs的激素受体活性。在测试的16个化合物中，6个和2个化合物分别在ERα和ERβ实验中显示出激动性活性，6个和6个化合物在这两个实验中显示出拮抗活性。4‘-HO-BDE-17通过ERα/β具有最强的雌激素样活性，4’-HO-BDE-49通过ERα/β具有最强的抗雌激素活性。在AR实验中，有13个化合物表现出拮抗活性，其中4‘-HO-BDE-17在10−8 M的低浓度下对AR介导的转录活性有抑制作用。在GR实验中，包括2个HO-PBDEs和2个MeO-PBDEs在内的7个化合物表现出较弱的拮抗活性。在TRBDE-1和TRBDE-1测定中，仅有4-HO-α-90有较弱的拮抗活性。综上所述，这些结果表明，PBDEs及其代谢产物可能通过核激素受体具有多种内分泌干扰作用，尤其是对HO-PBDEs具有比亲本PBDEs和相应的对位MeO-PBDEs更强的受体活性。
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. 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. We tested the hormone receptor activities of estrogen receptor α (ERα), ERβ, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor α1 (TRα1), and TRβ1 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. Of the 16 compounds tested, 6 and 2 showed agonistic activities in the ERα and ERβ assays, respectively, and 6 and 6 showed antagonistic activities in these assays. 4′-HO-BDE-17 showed the most potent estrogenic activity via ERα/β, and 4′-HO-BDE-49 showed the most potent anti estrogenic activity via ERα/β. 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 TRα1 and TRβ1 assays, only 4-HO-BDE-90 showed weak antagonistic activity. 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.
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影响因子：
10.4
作者：
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通讯作者：
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影响因子：
10.4
作者：
Meerts, IATM;Letcher, RJ;Hoving, S;Marsh, G;Bergman, Å;Lemmen, JG;van der Burg, B;Brouwer, A
通讯作者：
Brouwer, A