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  • Title: Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear receptors.
    Author: Kojima H, Takeuchi S, Sanoh S, Okuda K, Kitamura S, Uramaru N, Sugihara K, Yoshinari K.
    Journal: Toxicology; 2019 Feb 01; 413():48-55. PubMed ID: 30582956.
    Abstract:
    Several bisphenol A (BPA) analogues have been detected in environmental samples, foodstuffs, and/or human biological samples, and there is concern regarding their potential endocrine-disrupting effects. In this study, we characterized the agonistic and/or antagonistic activities of BPA and eight its analogues against human estrogen receptors (ERα/β), androgen receptor (AR), glucocorticoid receptor (GR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR). All the test compounds, except for bisphenol P (BPP), showed both ERα and ERβ agonistic activities, with bisphenol AF (BPAF) being the most potent. On the other hand, BPAF and BPP showed ERα and ERβ antagonistic activities. Interestingly, their ER activities demonstrated a preference toward ERβ. All the test compounds, except for bisphenol S, showed AR antagonistic activities, with bisphenol E being the most potent. Weak GR antagonistic activities were also found in BPA and five its analogues. PXR agonistic activity was observed in the six compounds, with bisphenol Z being the most potent. Results of the CAR assay revealed that BPA and five its analogues acted as CAR inverse agonists. Taken together, these results suggested that BPA analogues demonstrate multiple effects via human nuclear receptors in a similar manner to BPA, and several analogues might have more potent endocrine-disrupting activity than does BPA.
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