根据经济合作与发展组织的测试指南,确认了氰戊菊酯由类固醇激素受体介导的内分泌干扰潜能,以及雌激素受体α对脂质积累的依赖性影响。

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Da-Hyun Jeong , Da-Woon Jung , Hee-Seok Lee
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引用次数: 0

摘要

在本研究中,我们重点证实了拟除虫菊酯杀虫剂氰戊菊酯介导的类固醇激素受体内分泌干扰潜力,并揭示了其潜在机制。因此,我们按照经济合作与发展组织(OECD)的测试指南,利用荧光素酶报告器进行激素反应元件依赖性转录激活试验,在体外评估了雌激素受体-α(ERα)和雄激素受体(AR)介导的反应。我们观察到,氰戊菊酯通过ERα二聚化诱导细胞质ERα向细胞核转位,从而起到雌激素的作用,但它没有表现出AR介导的雄激素反应元件依赖性荧光素酶活性。此外,我们还证实,氰戊菊酯诱导的ERα活化会导致脂质积累,并在3个T3-L1脂肪细胞中以氰戊菊酯依赖的方式促进脂质积累。此外,芬戊酸酯诱导的脂质积累在ERα选择性拮抗剂的存在下受到抑制,而在糖皮质激素受体(GR)特异性抑制剂的存在下则不受影响。此外,研究还发现氰戊菊酯能刺激 3 T1-L1 脂肪细胞中促进脂质积累的转录因子的表达,而同时使用 ERα 选择性拮抗剂则能在 mRNA 和蛋白质水平上抑制脂肪生成/脂质生成转录因子的表达。这些研究结果表明,接触氰戊菊酯可能会通过干扰ERα活化依赖过程而导致脂质积累,从而引起ERα介导的内分泌干扰效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Confirmation of the steroid hormone receptor-mediated endocrine disrupting potential of fenvalerate following the Organization for Economic Cooperation and Development test guidelines, and its estrogen receptor α-dependent effects on lipid accumulation

Confirmation of the steroid hormone receptor-mediated endocrine disrupting potential of fenvalerate following the Organization for Economic Cooperation and Development test guidelines, and its estrogen receptor α-dependent effects on lipid accumulation

In this study, we focused on confirming the steroid hormone receptor-mediated endocrine-disrupting potential of the pyrethroid insecticide fenvalerate and unraveling the underlying mechanisms. Therefore, we assessed estrogen receptor-α (ERα)- and androgen receptor (AR)-mediated responses in vitro using a hormone response element-dependent transcription activation assay with a luciferase reporter following the Organization for Economic Cooperation and Development (OECD) test guidelines. We observed that fenvalerate acted as estrogen by inducing the translocation of cytosolic ERα to the nucleus via ERα dimerization, whereas it exhibited no AR-mediated androgen response element-dependent luciferase activity. Furthermore, we confirmed that fenvalerate-induced activation of ERα caused lipid accumulation, promoted in a fenvalerate-dependent manner in 3 T3-L1 adipocytes. Moreover, fenvalerate-induced lipid accumulation was inhibited in the presence of an ERα-selective antagonist, whereas it remained unaffected in the presence of a glucocorticoid receptor (GR)-specific inhibitor. In addition, fenvalerate was found to stimulate the expression of transcription factors that promote lipid accumulation in 3 T1-L1 adipocytes, and co-treatment with an ERα-selective antagonist suppressed adipogenic/ lipogenic transcription factors at both mRNA and protein levels. These findings suggest that fenvalerate exposure may lead to lipid accumulation by interfering with ERα activation-dependent processes, thus causing an ERα-mediated endocrine-disrupting effect.

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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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