In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles
Abstract Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processe...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55019-3 |
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| author | Asya Kadic Patricia Oles Benjamin Christian Fischer Anne Elisabeth Reetz Boubacar Sidiki Sylla Katreece Feiertag Vera Ritz Tanja Heise Philip Marx-Stoelting Tewes Tralau Kostja Renko Marize de Lourdes Marzo Solano |
| author_facet | Asya Kadic Patricia Oles Benjamin Christian Fischer Anne Elisabeth Reetz Boubacar Sidiki Sylla Katreece Feiertag Vera Ritz Tanja Heise Philip Marx-Stoelting Tewes Tralau Kostja Renko Marize de Lourdes Marzo Solano |
| author_sort | Asya Kadic |
| collection | DOAJ |
| description | Abstract Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1–DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA. |
| first_indexed | 2024-04-24T19:57:00Z |
| format | Article |
| id | doaj.art-59660257376f40a694545e90de68a965 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:57:00Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-59660257376f40a694545e90de68a9652024-03-24T12:18:48ZengNature PortfolioScientific Reports2045-23222024-03-0114111510.1038/s41598-024-55019-3In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazolesAsya Kadic0Patricia Oles1Benjamin Christian Fischer2Anne Elisabeth Reetz3Boubacar Sidiki Sylla4Katreece Feiertag5Vera Ritz6Tanja Heise7Philip Marx-Stoelting8Tewes Tralau9Kostja Renko10Marize de Lourdes Marzo Solano11Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R)Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR)Abstract Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1–DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.https://doi.org/10.1038/s41598-024-55019-3Thyroid hormone pathwayEndocrine disruptionAdverse outcomeThyroid networkPesticides |
| spellingShingle | Asya Kadic Patricia Oles Benjamin Christian Fischer Anne Elisabeth Reetz Boubacar Sidiki Sylla Katreece Feiertag Vera Ritz Tanja Heise Philip Marx-Stoelting Tewes Tralau Kostja Renko Marize de Lourdes Marzo Solano In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles Scientific Reports Thyroid hormone pathway Endocrine disruption Adverse outcome Thyroid network Pesticides |
| title | In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles |
| title_full | In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles |
| title_fullStr | In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles |
| title_full_unstemmed | In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles |
| title_short | In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles |
| title_sort | in vitro and in vivo investigation of a thyroid hormone system specific interaction with triazoles |
| topic | Thyroid hormone pathway Endocrine disruption Adverse outcome Thyroid network Pesticides |
| url | https://doi.org/10.1038/s41598-024-55019-3 |
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