Enantioselective endocrine-disrupting effects of bifenthrin on hormone synthesis in rat ovarian cells
Enantioselective endocrine-disrupting effects of bifenthrin on hormone synthesis in rat ovarian cells
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联苯菊酯对大鼠卵巢细胞激素合成的对映选择性内分泌干扰作用
DOI：
10.1016/j.tox.2011.08.016
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发表时间：
2011-11-28
期刊：
影响因子：
4.5
通讯作者：
Liu, Weiping
中科院分区：
文献类型：
--
作者：
Liu, Jing;Yang, Yan;Liu, Weiping
联苯菊酯（BF）是一种典型的手性农药，是一种广谱、广泛使用的拟除虫菊酯。BF异构体对映体选择性毒性的健康风险评价正受到越来越多的关注。在这项研究中，我们使用大鼠卵巢颗粒细胞作为体外模型，研究BF对映体对哺乳动物生殖关键的两种激素，孕酮和前列腺素E2（PGE 2）的生物合成的影响。我们发现，1 S-cis-BF，而不是1 R-cis-BF显着降低颗粒细胞的孕酮和PGE 2的分泌。BF的1 S-异构体降低了参与调节孕酮或PGE 2生物合成的限速步骤的基因P450 SCC、星星、PBR和DBI以及考克斯-2的表达。1 S-cis-BF可阻断星星和考克斯-2启动子的转录活性。此外，蛋白激酶C（PKC）的活性，一个重要的孕酮和PGE 2合成的信号介质，差异抑制1 S-cis-BF。分子对接结果表明，1 S-cis-BF与PKC蛋白之间形成了一个氢键。综上所述，本研究首次报道了BF异构体通过PKC途径对大鼠卵巢细胞孕酮和PGE 2合成的对映体选择性干扰作用。我们的研究结果表明，手性农药的对映选择性毒性应考虑评估哺乳动物生殖健康，在健康风险评估中非常关注的毒理学终点。皇冠版权所有（C）2011由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Bifenthrin (BF), a broad-spectrum and widely used synthetic pyrethroid, is a typical chiral pesticide. More attention is being paid to the health risk assessment of the enantioselective toxicity of BF isomers. In this study, we used rat ovarian granulosa cells as in vitro model to investigate effects of BF enantiomers on the biosynthesis of two hormones, progesterone and prostaglandin E2 (PGE2), which are critical for mammalian reproduction. We showed that 1S-cis-BF, but not 1R-cis-BF significantly decreased the secretion of progesterone and PGE2 in granulosa cells. 1S-isomer of BF reduced the expression of genes P450scc, StAR, PBR and DBI, as well as COX-2, which are involved in regulating the rate-limiting steps of progesterone or PGE2 biosynthesis. The transcriptional activation of StAR and COX-2 promoter were disrupted by 1S-cis-BF. Furthermore, activity of protein kinase C (PKC), an important signaling mediator of progesterone and PGE2 synthesis, was differentially inhibited by 1S-cis-BF. The data of molecular docking revealed that one hydrogen bond was formed between 1S-cis-BF and PKC protein. In conclusion, we firstly reported in this study the enantioselective disrupting effects of BF isomers on progesterone and PGE2 synthesis via PKC pathway in rat ovarian cells. Our findings suggest that the enantioselective toxicity of chiral pesticides should be considered for evaluating mammalian reproductive health, a toxicologic endpoint of great concern in health risk assessment. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.