ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Extrapolating In Vitro Screening Assay Data for Thyroperoxidase Inhibition to Predict Serum Thyroid Hormones in the Rat.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Disruption of the thyroid hormone system and patterns of altered thyroid hormones after gestational chemical exposures in rodents - a systematic review.Frontiers in endocrinology · 2023Pooled it
- Optimization of anToxicology reports · 2026Article
- Strategies for Signal Amplification of Thyroid Hormones via Electromigration Techniques Coupled with UV Detection and Laser-Induced Fluorescence.International journal of molecular sciences · 2025Article
- The common pathogenesis of nodular goiter in both sexes: An exploration into gene expression and signaling pathways.Heliyon · 2024Article
- Impact of methimazole-induced hypothyroidism on postnatal swine.Physiological reports · 2024Article
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- Cross species extrapolation of the disruption of thyroid hormone synthesis by oxyfluorfen using in vitro data, physiologically based pharmacokinetic (PBPK), and thyroid hormone kinetics models.Current research in toxicology · 2023Article
- A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins.Frontiers in endocrinology · 2023Article
- Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Mechanistic Computational Model for Extrapolating In Vitro Thyroid Peroxidase (TPO) Inhibition Data to Predict Serum Thyroid Hormone Levels in Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period.Scientific reports · 2021Article
- In vitro screening for chemical inhibition of the iodide recycling enzyme, iodotyrosine deiodinase.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- Regulation of Thyroid-disrupting Chemicals to Protect the Developing Brain.Endocrinology · 2020Review
- Targeted Pathway-based In Vivo Testing Using Thyroperoxidase Inhibition to Evaluate Plasma Thyroxine as a Surrogate Metric of Metamorphic Success in Model Amphibian Xenopus laevis.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Thyroperoxidase (TPO) is an enzyme essential for thyroid hormone (TH) synthesis and a target site for a number of xenobiotics that disrupt TH homeostasis. An in vitro high-throughput screening assay for TPO inhibition, the Amplex UltraRed-TPO (AUR-TPO), has been used to screen the ToxCast chemical libraries for this action. Output from this assay would be most useful if it could be readily translated into an in vivo response, namely a reduction of TH in serum. To this end, the relationship between TPO inhibition in vitro and serum TH decreases was examined in rats exposed to 2 classic TPO inhibitors, propylthiouracil (PTU) and methimazole (MMI). Serum and gland PTU, MMI, and TH levels were quantified using tandem liquid chromatography mass spectrometry. Thyroperoxidase activity was determined in thyroid gland microsomes treated with PTU or MMI in vitro and ex vivo from thyroid gland microsomes prepared from exposed animals. A quantitative model was constructed by contrasting in vitro and ex vivo AUR-TPO results and the in vivo time-course and dose-response analysis. In vitro:ex vivo correlations of AUR-TPO outputs indicated that less than 30% inhibition of TPO in vitro was sufficient to reduce serum T4 by 20%, a degree of regulatory significance. Although further testing of model estimates using other TPO inhibitors is essential for verification of these initial findings, the results of this study provide a means to translate in vitro screening assay results into predictions of in vivo serum T4 changes to inform risk assessment.
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