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  • 标题:In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors
  • 本地全文:下载
  • 作者:Yanis Zekri ; Laure Dall Agnol ; Frédéric Flamant
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2021
  • 卷号:24
  • 期号:9
  • 页码:1-21
  • DOI:10.1016/j.isci.2021.102957
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryChemicals acting as thyroid hormone disruptors (THDs) are of a particular concern for public health, considering the importance of this hormone in neurodevelopment and metabolic processes. They might either alter the circulating level of thyroid hormone (TH) or interfere with the cellular response to the hormonal stimulation. In order to assess this later possibility we selected 39 pesticides and combined severalin vitrotests. Reporter assays respectively addressed the transactivation capacity of the full-length TH nuclear receptor TRα1, the transactivation capacity of its C-terminal ligand binding domain, or the ability of the hormone to destabilize the interaction between TRα1 and the transcriptional corepressor NcoR. Although some pesticides elicit a cellular response, which sometimes interferes with TH signaling, RNA-seq analysis provided no evidence that they can act as TRα1 agonists or antagonists. Their neurodevelopmental toxicity in mammals cannot be explained by an alteration of the response to TH.Graphical abstractDisplay OmittedHighlights•Pesticides were tested for their capacity to interfere with thyroid hormone receptors•Three reporter assays were combined to identify possible agonists/antagonists•The tested pesticides are not major disruptors of thyroid hormone signalingBiological sciences; Toxicology; Environmental toxicology
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