Publikationsdatenbank

In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles (2024)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Kadic, Asya

Oles, Patricia

Fischer, Benjamin Christian

Reetz, Anne Elisabeth (WE 12)

Sylla, Boubacar Sidiki

Feiertag, Katreece

Ritz, Vera

Heise, Tanja

Marx-Stoelting, Philip

Tralau, Tewes

Renko, Kostja

Solano, Marize de Lourdes Marzo

Quelle

Scientific reports

Bandzählung: 14

Heftzählung: 1

Seiten: 6503

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41598-024-55019-3

DOI: 10.1038/s41598-024-55019-3

Pubmed: 38499550

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.