Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200292, China.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Ecotoxicol Environ Saf. 2021 Sep 1;220:112389. doi: 10.1016/j.ecoenv.2021.112389. Epub 2021 May 31.
Triclosan (TCS) is an endocrine-disrupting chemical (EDC), which is used ubiquitously as an antimicrobial ingredient in healthcare products and causes contamination in the environment such as air, water, and biosolid-amended soil. Exposure to TCS may increase the risk of reproduction diseases and health issues. Several groups, including ours, have proved that TCS increased the biosynthesis of steroid hormones in different types of steroidogenic cells. However, the precise mechanism of toxic action of TCS on increased steroidogenesis at a molecular level remains to be elucidated. In this study, we try to address the mode of action that TCS affects energy metabolism with increased steroidogenesis. We evaluated the adverse effects of TCS on energy metabolism and steroidogenesis in human ovarian granulosa cells. The goal is to elucidate how increased steroidogenesis can occur with a shortage of adenosine triphosphate (ATP) whereas mitochondria-based energy metabolism is impaired. Our results demonstrated TCS increased estradiol and progesterone levels with upregulated steroidogenesis gene expression at concentrations ranging from 0 to 10 µM. Besides, glucose consumption, lactate level, and pyruvate kinase transcription were increased. Interestingly, the lactate level was attenuated with increased steroidogenesis, suggesting that pyruvate fate was shifted away from the formation of lactate towards steroidogenesis. Our study is gathering evidence suggesting a mode of action that TCS changes energy metabolism by predominating glucose flow towards the biosynthesis of steroid hormones. To the best of our knowledge, this is the first report that TCS presents such toxic action in disrupting hormone homeostasis.
三氯生（TCS）是一种内分泌干扰化学物质（EDC），作为一种抗菌成分被广泛应用于医疗保健产品中，并导致空气、水和生物固体改良土壤等环境受到污染。接触 TCS 可能会增加生殖疾病和健康问题的风险。包括我们在内的几个研究小组已经证明，TCS 会增加不同类型的类固醇生成细胞中类固醇激素的生物合成。然而，TCS 在分子水平上对增加类固醇生成的毒性作用的确切机制仍有待阐明。在这项研究中，我们试图确定 TCS 影响类固醇生成增加的能量代谢的作用模式。我们评估了 TCS 对人卵巢颗粒细胞能量代谢和类固醇生成的不良影响。目的是阐明在破坏基于线粒体的能量代谢的情况下，类固醇生成增加如何发生。我们的结果表明，TCS 在浓度为 0 至 10 μM 的范围内，可增加雌二醇和孕酮水平，并上调类固醇生成基因表达，从而增加类固醇生成。此外，葡萄糖消耗、乳酸水平和丙酮酸激酶转录增加。有趣的是，随着类固醇生成的增加，乳酸水平降低，表明丙酮酸的命运从形成乳酸转向类固醇生成。我们的研究提供了证据，表明 TCS 通过将葡萄糖流量主要转向类固醇激素的生物合成来改变能量代谢。据我们所知，这是首次报道 TCS 在破坏激素平衡方面存在这种毒性作用。
