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  • Title: Characterization of steroid hormone receptor activities in 100 hydroxylated polychlorinated biphenyls, including congeners identified in humans.
    Author: Takeuchi S, Shiraishi F, Kitamura S, Kuroki H, Jin K, Kojima H.
    Journal: Toxicology; 2011 Nov 18; 289(2-3):112-21. PubMed ID: 21843587.
    Abstract:
    Hydroxylated polychlorinated biphenyls (OH-PCBs), major metabolites of PCBs, have been reported to act as estrogen receptor α (ERα) agonists or antagonists. However, little concern has been paid to the ability of OH-PCBs to interfere with other steroid hormone receptors such as ERβ, androgen receptor (AR) or glucocorticoid receptor (GR). In this study, we characterized the agonistic and antagonistic activities of available 100 OH-PCBs (39 ortho-, 24 meta-, and 37 para-OH compounds), including some congeners identified in humans, against human ERα/β, AR, and GR using in vitro reporter gene assays. In the ERα assay, 45 and 9 of the 100 OH-PCBs tested showed agonistic and antagonistic activities, respectively. In the ERβ assay, 45 and 6 compounds showed agonistic and antagonistic activities, respectively. In the AR and GR assays, although none of the compounds tested showed agonistic activity, 83 and 30 of the 100 OH-PCBs showed antagonistic activity, respectively. These AR and/or GR antagonistic compounds had various patterns of substituent in the structure, while relatively potent ERα/β agonistic and antagonistic compounds possessed para- and ortho-OH structures, respectively. Three OH-PCBs, predominantly identified in human tissues, showed little ERα/β or AR activities, apart from the weak ERα and/or GR antagonistic activity observed in 4-OH-CB107 and 4-OH-CB187. Taken together, these results suggest that a large number of OH-PCBs might act as agonists and/or antagonists against ERα/β, AR and GR.
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