Profiling of bisphenol S towards nuclear receptors activities in human reporter cell lines

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 (IC₅₀=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.