九种有机磷酸酯阻燃剂的潜在糖皮质激素和盐皮质激素作用,Environmental Science & Technology

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九种有机磷酸酯阻燃剂的潜在糖皮质激素和盐皮质激素作用
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2017-04-21 00:00:00 , DOI: 10.1021/acs.est.7b01237
Quan Zhang _{1,

2} , Jinghua Wang ₁ , Jianqiang Zhu ₁ , Jing Liu ₃ , Meirong Zhao _{1,

2}

Affiliation

有机磷阻燃剂（OPFRs）作为多溴二苯醚（PBDEs）的替代品，已在环境和生物区系中被频繁检测到，并可能对生物造成不利影响。然而，关于OPFR的潜在内分泌破坏的信息，尤其是其对类固醇激素受体如糖皮质激素和盐皮质激素受体（GR / MR）的作用是有限的。在这项研究中，通过GR / MR和H295R类固醇生成分析的双重荧光素酶报告基因被用来评估9种OPFR的内分泌破坏。我们发现TMPP，TPHP和TDBPP均具有GR和MR拮抗活性，而TNBP和TDCIPP仅在10 ^–8至10 ^–5的浓度范围内具有MR拮抗作用。摩尔/升（M）。在H295R类固醇生成试验中，进一步研究了响应OPFRs的八个类固醇生成基因的倍数变化。我们发现在浓度为2×10 – ⁶ M的TMPP，TPHP或TDBPP暴露后，CYP17，CYP21和CYP11B1的表达显着下调。同时，TMPP减少了皮质醇的产生，TDBPP下调了醛固酮的分泌。我们的结果表明，某些OPFRs可以与GR和MR相互作用，并有可能干扰类固醇生成。此处提供的数据将有助于全面了解OPFR的潜在内分泌干扰。

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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 CYP17,CYP21, and CYP11B1 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.

更新日期：2017-05-02

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