School of Public Health, Hangzhou Medical College, Hangzhou 310013, China.
Department of Public Health, Yu Hang No.2 People's Hospital, Hangzhou 311100, China.
Environ Toxicol Pharmacol. 2022 Jan;89:103784. doi: 10.1016/j.etap.2021.103784. Epub 2021 Dec 9.
Cis-bifenthrin (cis-BF) is a common-used pyrethroid insecticide frequently detected in environmental and biological matrices. Mounting evidence highlights the endocrine disrupting effects of cis-BF due to anti-estrogenic or anti-androgenic activity. However, little is known about the exposure effects of cis-BF on adrenal cortex function. In this study, effects of cis-BF on biosynthesis of adrenal steroids, as well as the potential mechanisms were investigated in human adrenocortical carcinoma (H295R) cells. Cis-BF decreased basal production levels of cortisol and aldosterone, as well as cAMP-induced production of cortisol. Both he basal and cAMP-stimulated transcriptional levels of several steroidogenic genes were significantly down-regulated by cis-BF. As an important rate-limiting enzyme in steroidogenesis, the protein level of StAR was prohibited by cis-BF on both basal and cAMP-induced conditions. Intracellular level of cAMP was significantly reduced by cis-BF. Overall, these data suggest that cis-BF may inhibit the biosynthesis of cortisol and aldosterone via disrupting cAMP signaling cascade.
顺式氯菊酯（cis-BF）是一种常用的拟除虫菊酯类杀虫剂，经常在环境和生物基质中检测到。越来越多的证据表明，由于抗雌激素或抗雄激素活性，cis-BF 具有内分泌干扰作用。然而，关于 cis-BF 对肾上腺皮质功能的暴露效应知之甚少。在这项研究中，研究了 cis-BF 对人肾上腺皮质癌细胞（H295R）中肾上腺类固醇生物合成以及潜在机制的影响。cis-BF 降低了皮质醇和醛固酮的基础产生水平，以及 cAMP 诱导的皮质醇产生。cis-BF 显著下调了几种类固醇生成基因的基础和 cAMP 刺激转录水平。作为类固醇生成中的重要限速酶，StAR 蛋白水平在 cis-BF 的基础和 cAMP 诱导条件下均受到抑制。cis-BF 显著降低了细胞内 cAMP 水平。总的来说，这些数据表明，cis-BF 可能通过破坏 cAMP 信号级联来抑制皮质醇和醛固酮的生物合成。
