Study of eighteen typical bisphenol analogues as agonist or antagonist for androgen and glucocorticoid at sub-micromolar concentrations in vitro

Bisphenol A and its substitutions are commonly used to manufacture epoxy resins, plastic materials and different kinds of daily necessities. In this process, a large number of bisphenol analogues (BPs) are continuously released directly/in-directly into the environment. Through the chain of environment-feed-farmed-animals-livestock and poultry prod-ucts, BPs present the low concentration but chronic exposure for surroundings and environment. In addition, BPs have been revealed by extensive studies as emerging endocrine disruptors, whose effects on androgens/glucocorti-coids have rarely been mentioned in previous reports. The (anta-) agonist/antagonist properties of 18 classic BPs were investigated in vitro: We assessed the cytotoxicity and examined the luciferase induction values of BPs in MDA-kb2 cells, incubated single or co-incubated with dihydrotestosterone (DHT), dexamethasone, flutamide and RU486 for 24 h. From the concentration of 10-10 to 10-5 M, BPs had negligible cytotoxicity for MDA-kb2 cells, except for 4,4'-(9-Fluorenylidene)diphenol with the IC501.32 mu M. All 18 BPs had the response to androgen/glucocorticoid recep-tors (AR/GR). BPs at nanomolar and trace concentrations are agonists, while BPs at micromolar and higher concentra-tions are antagonists. Molecular docking showed that BPs interact with AR/GR through hydrophobic bonds, hydrogen bonds, T-type pi-stacking and water-bridge. These experimental data demonstrate the universality of the endocrine-disrupting effects of BPs and suggest the urgency of paying attention to the usages of BPs.