AI Article Synopsis
- Thyroid hormone (TH) synthesis in zebrafish requires hydrogen peroxide from NADPH oxidases DUOX1 and DUOX2 along with maturation factors DUOXA1 and DUOXA2.
- Using a thyroid-specific reporter, researchers found that mutants lacking these genes exhibited hypothyroid symptoms and goiter due to impaired TH production.
- Treatment with the NADPH oxidase inhibitor VAS2870 replicated the thyroid issues seen in mutant zebrafish, demonstrating its potential as a model to study thyroid function disruptors.
Article Abstract
Thyroid hormone (TH) synthesis requires extracellular hydrogen peroxide generated by the NADPH oxidases, DUOX1 and DUOX2, with maturation factors, DUOXA1 and DUOXA2. In zebrafish, only one duox and one duoxa gene are present. Using a thyroid-specific reporter line, we investigated the role of Duox and Duoxa for TH biosynthesis in zebrafish larvae. Analysis of several zebrafish duox and duoxa mutant models consistently recovered hypothyroid phenotypes with hyperplastic goiter caused by impaired TH synthesis. Mutant larvae developed enlarged thyroids and showed increased expression of the EGFP reporter and thyroid functional markers including wild-type and mutated duox and duoxa transcripts. Treatment of zebrafish larvae with the NADPH oxidase inhibitor VAS2870 phenocopied the thyroid effects observed in duox or duoxa mutants. Additional functional in vitro assays corroborated the pharmacological inhibition of Duox activity by VAS2870. These data support the utility of this new experimental model to characterize endocrine disruptors of the thyroid function.
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| http://dx.doi.org/10.1016/j.mce.2019.110635 | DOI Listing |
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Article Synopsis
- Thyroid hormone (TH) synthesis in zebrafish requires hydrogen peroxide from NADPH oxidases DUOX1 and DUOX2 along with maturation factors DUOXA1 and DUOXA2.
- Using a thyroid-specific reporter, researchers found that mutants lacking these genes exhibited hypothyroid symptoms and goiter due to impaired TH production.
- Treatment with the NADPH oxidase inhibitor VAS2870 replicated the thyroid issues seen in mutant zebrafish, demonstrating its potential as a model to study thyroid function disruptors.
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