Laboratory of Medical Investigations, San Cecilio University Hospital, University of Granada, Cíber en Epidemiología y Salud Pública (CIBERESP), Granada E-18071, Spain.
Toxicol Appl Pharmacol. 2013 Oct 1;272(1):127-36. doi: 10.1016/j.taap.2013.05.015. Epub 2013 May 25.
Bisphenols are a group of chemicals structurally similar to bisphenol-A (BPA) in current use as the primary raw material in the production of polycarbonate and epoxy resins. Some bisphenols are intended to replace BPA in several industrial applications. This is the case of bisphenol-S (BPS), which has an excellent stability at high temperature and resistance to sunlight. Studies on the endocrine properties of BPS have focused on its interaction with human estrogen receptor alpha (hERα), but information on its interaction with other nuclear receptors is scarce. The aim of this study was to investigate interactions of BPS, BPF, BPA and its halogenated derivatives, tetrachlorobisphenol A (TCBPA), and tetrabromobisphenol A (TBBPA), with human estrogen receptors (hERα and hERβ), androgen receptor (hAR), and pregnane X receptor (hPXR), using a panel of in vitro bioassays based on competitive binding to nuclear receptors (NRs), reporter gene expression, and cell proliferation assessment. BPS, BPF, and BPA efficiently activated both ERs, while TCBPA behaved as weak hERα agonist. Unlike BPF and BPA, BPS was more active in the hERβ versus hERα assay. BPF and BPA were full hAR antagonists (BPA>BPF), whereas BPA and BPS were weak hAR agonists. Only BPA, TCBPA, and TBBPA, were hPXR agonists (TCBPA>TBBPA>BPA). These findings provide evidence that BPA congeners and derivatives disrupt multiple NRs and may therefore interfere with the endocrine system. Hence, further research is needed to evaluate the potential endocrine-disrupting activity of putative BPA substitutes.
双酚类物质是一组化学物质，其结构与目前用作生产聚碳酸酯和环氧树脂主要原料的双酚 A（BPA）相似。一些双酚类物质旨在替代几种工业应用中的 BPA。双酚 S（BPS）就是这种情况，它在高温和耐阳光方面具有极好的稳定性。关于 BPS 内分泌特性的研究集中在其与人雌激素受体α（hERα）的相互作用上，但关于其与其他核受体相互作用的信息却很少。本研究旨在使用基于核受体（NRs）竞争性结合、报告基因表达和细胞增殖评估的体外生物测定法，研究 BPS、BPF、BPA 及其卤代衍生物四氯双酚 A（TCBPA）和四溴双酚 A（TBBPA）与人雌激素受体（hERα和 hERβ）、雄激素受体（hAR）和孕烷 X 受体（hPXR）的相互作用。BPS、BPF 和 BPA 有效地激活了两种 ER，而 TCBPA 则表现为弱 hERα激动剂。与 BPF 和 BPA 不同，BPS 在 hERβ与 hERα测定中更活跃。BPF 和 BPA 是完全的 hAR 拮抗剂（BPA>BPF），而 BPA 和 BPS 是弱的 hAR 激动剂。只有 BPA、TCBPA 和 TBBPA 是 hPXR 激动剂（TCBPA>TBBPA>BPA）。这些发现提供了证据，表明 BPA 同系物和衍生物会破坏多种 NRs，因此可能会干扰内分泌系统。因此，需要进一步研究来评估潜在的 BPA 替代品的内分泌干扰活性。
