In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors
Summary: Chemicals 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 r...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221009251 |
| _version_ | 1819103482602323968 |
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| author | Yanis Zekri Laure Dall Agnol Frédéric Flamant Romain Guyot |
| author_facet | Yanis Zekri Laure Dall Agnol Frédéric Flamant Romain Guyot |
| author_sort | Yanis Zekri |
| collection | DOAJ |
| description | Summary: Chemicals 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 several in vitro tests. 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. |
| first_indexed | 2024-12-22T01:51:10Z |
| format | Article |
| id | doaj.art-848a482ea0a24a1387dce030ed2b496f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-22T01:51:10Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-848a482ea0a24a1387dce030ed2b496f2022-12-21T18:42:55ZengElsevieriScience2589-00422021-09-01249102957In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptorsYanis Zekri0Laure Dall Agnol1Frédéric Flamant2Romain Guyot3Institut de Génomique Fonctionnelle de Lyon, Univ Lyon, CNRS UMR 5242, INRAE USC 1370 École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 46 allee d'Italie, 69364 Lyon, FranceInstitut de Génomique Fonctionnelle de Lyon, Univ Lyon, CNRS UMR 5242, INRAE USC 1370 École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 46 allee d'Italie, 69364 Lyon, FranceInstitut de Génomique Fonctionnelle de Lyon, Univ Lyon, CNRS UMR 5242, INRAE USC 1370 École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 46 allee d'Italie, 69364 Lyon, France; Corresponding authorInstitut de Génomique Fonctionnelle de Lyon, Univ Lyon, CNRS UMR 5242, INRAE USC 1370 École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 46 allee d'Italie, 69364 Lyon, FranceSummary: Chemicals 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 several in vitro tests. 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.http://www.sciencedirect.com/science/article/pii/S2589004221009251biological sciencestoxicologyenvironmental toxicology |
| spellingShingle | Yanis Zekri Laure Dall Agnol Frédéric Flamant Romain Guyot In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors iScience biological sciences toxicology environmental toxicology |
| title | In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors |
| title_full | In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors |
| title_fullStr | In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors |
| title_full_unstemmed | In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors |
| title_short | In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors |
| title_sort | in vitro assessment of pesticides capacity to act as agonists antagonists of the thyroid hormone nuclear receptors |
| topic | biological sciences toxicology environmental toxicology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221009251 |
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