State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
State Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Beijing Key Laboratory of Industrial Wastewater Treatment and Reuse, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Sci Total Environ. 2020 May 10;716:136987. doi: 10.1016/j.scitotenv.2020.136987. Epub 2020 Feb 4.
The present study aimed to evaluate the thyroid-disrupting potency of chlordecone, and reveal the underlying mechanism. In the in vivo assays, rare minnow embryos were exposed to 0, 0.01, 0.1, 1 and 10 μg·L chlordecone until sexually mature. The results showed decreased T4 but increased T3 concentrations in plasma, upregulated mRNA levels of thyrotropin-releasing hormone receptor (trhr) and sodium-iodide symporter (nis) in the brain, and transthyretin (ttr), thyroid hormone receptor α (trα) and deiodinase enzymes (dio1 and dio2) in the liver of adult fish. In the in vitro assays, single chlordecone treatments promoted growth hormone (GH) and prolactin (PRL) secretion in GH3 cells. Transcription of thyroid receptor (trβ) was inhibited, but this is not likely responsible for chlordecone-induced GH secretion and altered transcription. When co-treated with T3, chlordecone acted independently of the effect of T3 on GH secretion; chlordecone-induced GH/PRL secretion and mRNA expression were further promoted when co-treated with E2, but inhibited when co-treated with ICI, indicating an important role for estrogen receptors (ERs) in chlordecone-induced changes in GH3 cells. Furthermore, in silico prediction suggested no stable interactions between chlordecone and thyroid hormone-related proteins, as well as a regulatory role for ERs in thyroid systems. Overall, our results indicated that chlordecone may have adverse effects on thyroid systems upon long-term exposure. However, rather of TRs, ERs may be responsible for thyroid disruption following chlordecone exposure.
本研究旨在评估十氯酮的甲状腺干扰能力，并揭示其潜在机制。在体内试验中，稀有鲫鱼胚胎在 0、0.01、0.1、1 和 10μg·L 十氯酮中暴露至性成熟。结果表明，血浆中 T4 浓度降低，T3 浓度升高，脑内促甲状腺激素释放激素受体 (trhr) 和钠碘转运体 (nis) 的 mRNA 水平上调，肝脏中转甲状腺素蛋白 (ttr)、甲状腺激素受体 α (trα) 和脱碘酶 (dio1 和 dio2) 的 mRNA 水平上调。在体外试验中，十氯酮单一处理可促进 GH3 细胞生长激素 (GH) 和催乳素 (PRL) 的分泌。甲状腺受体 (trβ) 的转录受到抑制，但这可能不是十氯酮诱导 GH 分泌和改变转录的原因。当与 T3 共同处理时，十氯酮的作用独立于 T3 对 GH 分泌的影响；当与 E2 共同处理时，十氯酮诱导的 GH/PRL 分泌和 mRNA 表达进一步增强，但当与 ICI 共同处理时，十氯酮诱导的 GH3 细胞 GH/PRL 分泌和 mRNA 表达受到抑制，表明雌激素受体 (ERs) 在十氯酮诱导的 GH3 细胞变化中起重要作用。此外，计算机预测表明，十氯酮与甲状腺激素相关蛋白之间没有稳定的相互作用，以及 ERs 在甲状腺系统中的调节作用。总的来说，我们的结果表明，十氯酮长期暴露可能对甲状腺系统产生不良影响。然而，在十氯酮暴露后，可能是 ERs 而不是 TRs 负责甲状腺的破坏。
