Endocrine Abstracts

Background: Bisphenol A (BPA) acts as an endocrine disruptor in different endocrine systmes. However, its impact on the adrenal cortex and steroidogenesis is largely unknown. This also applies to its substitute substances bisphenol F (BPF) and S (BPS). Therefore, experiments addressing this subject are urgently needed.

Methods: The human adrenocortical cell lines NCI-H295R and MUC-1 were treated with increasing concentrations (1 nM–1 mM) of bisphenol A, F, and S. Concentrations of fifteen adrenal steroids in cell supernatants were measured via liquid-chromatography–tandem-mass spectrometry (LC–MS/MS) after different periods of exposure (24 h, 72 h). Cell viability was monitored to assess cytotoxicity.

Results: All tested bisphenols are able to interfere with steroid production compared to untreated cells in a dose- and time-dependent manner in both cell lines: in the NCI-H295R hormone levels of 11-deoxycortisol, testosterone, androstenedione, dihydrotestosterone, cortisol and cortison were significantly decreased after 72 hours of exposure (at >100 μM BPA, BPF and BPS respectively, P<0.05). For instance, 100μM BPA treatment resulted in a 0.29-fold decrease of testosterone, and a 0.43-fold decrease of cortison. Interestingly, tested bisphenols showed ambiguous effects on some parameters, e.g. a 0.39-fold decrease of progesterone was detected in 100 μM BPA, while BPF led to a 26-fold increase. Furthermore, we found an increased level of estradiol, 21-deoxycortisol and 17-hydroxyprogesterone in BPF-treated cells (P<0.05). At large, reported effects were confirmed in MUC-1 cells, which seem to be more resilient against tested bisphenols. In this sense, calculated median lethal doses (LD₅₀) were: BPA 110.1 μM, BPS 229.4 μM, BPF 344.5 μM for NCI-H295R and BPA 279.4 μM BPF 356.8 μM and BPS 1.31mM for MUC-1.

Conclusions: Our results provide further evidence that bisphenol A, F, and S act as disruptors of steroidogenesis and steroid secretion. Underlying mechanisms and pathways are yet to investigate. This reinforces the need for further research efforts focusing on EDCs’ effects on the adrenal gland.