EYES2023 ESE Young Endocrinologists and Scientists (EYES) 2023 Oral communication 8: Interdisciplinary Endocrinology and Environment, Society and Governance (4 abstracts)
1Uniklinikum Würzburg, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Germany, Endokrinologie und Diabetologie, Würzburg, Germany; 2Uniklinikum Würzburg, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Germany, Medizinische Klinik und Poliklinik I Endokrinologie, Würzburg, Germany; 3Department of Medicine I, University Hospital Würzburg, University Hospital of Wuerzburg, Würzburg, Germany; 4University Hospital Würzburg, Medizinische Klinik I, Division of Endocrinology and Diabetes, Würzburg, Germany; 5Core Unit Clinical Mass Spectrometry, Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Germany, Endokrinologie, Würzburg, Germany; 6University Hospital Würzburg; Medizinische Klinik I; Division of Endocrinology and Diabetes, Würzburg, Germany, 1department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Germany, Endocrinology, Würzburg, Germany.
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 nM1 mM) of bisphenol A, F, and S. Concentrations of fifteen adrenal steroids in cell supernatants were measured via liquid-chromatographytandem-mass spectrometry (LCMS/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.