Effects of bisphenol analogues on steroidogenic gene expression and hormone synthesis in H295R cells

The use of Bisphenol A (BPA) has been regulated in many countries because of its potential adverse effects on human health. As a result of the restriction, structural anologues such as bisphenol S (BPS) and bisphenol F (BPF) have already been used for industrial applications as alternatives to BPA. Bisphenol AF (BPAF) is mainly used as a crosslinker in the synthesis of specialty fluoroelastomers. These compounds have been detected in various environmental matrices and human samples. Previous studies have shown that these compounds have potential endocrine disrupting effects on wildlife and mammals in general. However, the effects on adrenocortical function and the underlying mechanisms are not fully understood. In the present study, the H295R cell line was used as a model to compare the cell toxicity and to investigate the potential endocrine disrupting action of four BPs (including BPA, BPS, BPF, and BPAF). The half lethal concentration (LC50) values at 72 h exposure indicated that the rank order of toxicities of the chemicals was BPAF > BPA > BPS > BPF. The hormone results demonstrated that BPA analogues, such as BPF, BPS and BPAF were capable of altering steroidogenesis in H295R cells. BPA and BPS exhibited inhibition of hormone production, BPF predominantly led to increased progesterone and 17β-estradiol levels and BPAF showed induction of progesterone and reduction of testosterone. Inhibition effects of BPA and BPAF on hormone production were probably mediated by down-regulation of steroidogenic genes in H295R cells. However, the mechanisms of the endocrine interrupting action of BPF and BPS are still unclear, which may have additional mechanisms that have not been detected with BPA.