Zenata Ondrej, Dvorak Zdenek, Vrzal Radim
Department of Cell Biology Genetics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 27, Olomouc, CZ-783 71, Czech Republic.
Department of Cell Biology Genetics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 27, Olomouc, CZ-783 71, Czech Republic.
Toxicol Lett. 2017 Nov 5;281:10-19. doi: 10.1016/j.toxlet.2017.09.006. Epub 2017 Sep 12.
Bisphenol S (BPS) is heat-stable structural analog of bisphenol A (BPA), a known endocrine disruptor. Due to the effort to replace BPA with BPS, it is essential to know if BPS is suitable non-toxic replacement without reported deleterious effects of BPA. Since most of the BPA effects are ascribed to its ability to activate nuclear receptors, we screened some prominent members of this family in order to confirm or refute some recent findings. We found that BPS insignificantly activated aryl hydrocarbon receptor (AhR) in reporter gene assay and no induction of AhR target gene CYP1A1 was observed in human hepatocytes (HH). BPS was able to act like an antagonist of pregnane X receptor (PXR) in reporter gene assay, but the expression of PXR target gene CYP3A4, was only moderately affected in HH. While BPS antagonized dexamethasone-inducible glucocorticoid receptor (GR)-dependent luciferase activity in reporter gene assay (IC=52μM), it was not able to antagonize dexamethasone effects on GR-target genes, including GILZ, NFKBIA and IL-6. Synergistic effect of BPS (range 0.001-100μM) and DHT (100nM) was observed at androgen receptor (AR) activity level only. In conclusion, we show that BPS had only limited effect on tested nuclear receptors. Moreover, submicromolar concentrations of BPS affected activated AR. Thus, due to the low levels of exposure for humans, BPS is probably of no regulatory concern. However, further investigation should delineate possible impact on male/female development or sexual functions.
双酚S（BPS）是双酚A（BPA）的热稳定结构类似物，双酚A是一种已知的内分泌干扰物。由于人们努力用BPS替代BPA，因此有必要了解BPS是否是合适的无毒替代品，且不存在BPA所报道的有害影响。由于大多数BPA的作用归因于其激活核受体的能力，我们筛选了该家族的一些重要成员，以证实或反驳一些最近的研究发现。我们发现，在报告基因测定中，BPS对芳烃受体（AhR）的激活作用不显著，在人肝细胞（HH）中未观察到AhR靶基因CYP1A1的诱导。在报告基因测定中，BPS能够像孕烷X受体（PXR）的拮抗剂一样发挥作用，但PXR靶基因CYP3A4的表达在HH中仅受到中度影响。虽然在报告基因测定中BPS拮抗地塞米松诱导的糖皮质激素受体（GR）依赖性荧光素酶活性（IC = 52μM），但它不能拮抗地塞米松对GR靶基因的作用，包括GILZ、NFKBIA和IL-6。仅在雄激素受体（AR）活性水平观察到BPS（浓度范围为0.001 - 100μM）和双氢睾酮（DHT，100nM）的协同作用。总之，我们表明BPS对所测试的核受体只有有限的影响。此外，亚微摩尔浓度的BPS会影响激活的AR。因此，由于人类接触BPS的水平较低，BPS可能无需监管关注。然而，进一步的研究应阐明其对男性/女性发育或性功能可能产生的影响。
