Potential Glucocorticoid and Mineralocorticoid Effects of Nine Organophosphate Flame Retardants

Organophosphate flame retardants (OPFRs), as alternatives of polybrominated diphenyl ethers (PBDEs), have been frequently detected in the environment and biota, and could pose adverse effects on organisms. However, information on the potential endocrine disruption of OPFRs, especially their effects on steroid hormone receptors, such as glucocorticoid and mineralocorticoid receptors (GR/MR), is limited. In this study, the dual-luciferase reporter gene assay via GR/MR and a H295R steroidogenesis assay were employed to evaluate the endocrine disruption of nine OPFRs. We found TMPP, TPHP, and TDBPP exhibited both GR and MR antagonistic activities, while TNBP and TDCIPP only showed MR antagonistic property within a concentration range of 10^–8 to 10^–5 mol/L­(M). In the H295R steroidogenesis assay, the fold changes of eight steroidogenic genes in response to OPFRs were further studied. We found <i>CYP17</i>,<i>CYP21</i>, and <i>CYP11B1</i> expression were significantly down-regulated following TMPP, TPHP, or TDBPP exposure at a concentration of 2 × 10^–6 M. Meanwhile TMPP decreased the production of cortisol and TDBPP down-regulated the secretion of aldosterone. Our results indicate that some OPFRs can interact with GR and MR, and have the potential to disturb steroidogenesis. Data provided here will be helpful to comprehensively understand the potential endocrine disruption of OPFRs