Evaluation of a panel of in vitro methods for assessing thyroid receptor β and transthyretin transporter disrupting activities

Bérénice Collet; Eszter Simon; Sander van der Linden; Nadia el Abdellaoui; Matthijs Naderman; Hai yen Man; Irene Middelhof; Bart van der Burg; Harrie Besselink; Abraham Brouwer

doi:10.1016/j.reprotox.2019.05.011

Evaluation of a panel of in vitro methods for assessing thyroid receptor β and transthyretin transporter disrupting activities

Bérénice Collet^*, Eszter Simon, Sander van der Linden, Nadia el Abdellaoui, Matthijs Naderman, Hai yen Man, Irene Middelhof, Bart van der Burg, Harrie Besselink, Abraham Brouwer

^*Corresponding author for this work

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Abstract

We developed a thyroid testing panel to assess endocrine disrupting chemicals (EDCs) capacities to bind either the thyroid receptor β (TRβ) or the thyroid hormones transporter transthyretin (TTR). We first stably transfected a human U2OS cell line with TRβ and a luciferase reporter construct to develop the TRβ CALUX® reporter gene assay to assess chemicals’ potential to interact with TRβ. Secondly, we combined a TTR-binding assay with the TRβ CALUX (TTR-TRβ CALUX) and optimized the system to evaluate the competitive properties of EDCs towards T4 for TTR binding. Both systems were evaluated with a range of known thyroid-disrupting compounds. The agonistic/antagonistic TRβ CALUX successfully predicted 9/9 and 9/12 test compounds, respectively. The TTR-TRβ CALUX predicted 9/9 compounds and demonstrated competitive activities when analyzing waste water samples. We concluded that the proposed test battery is a promising screening method able to efficiently generate data on thyroid hormone interferences by chemicals.

Original language	English
Pages (from-to)	432-444
Number of pages	13
Journal	Reproductive Toxicology
Volume	96
Early online date	8 May 2019
DOIs	https://doi.org/10.1016/j.reprotox.2019.05.011
Publication status	Published - Sept 2020

Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 722634 .

Funders	Funder number
European Union's Horizon 2020 research and innovation program
European Union’s Horizon 2020 research and innovation program
Marie Sklodowska-Curie	722634

Keywords

Bioassay
CALUX
Endocrine disruption
Thyroid hormones
TTR binding potency
Water extract

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.reprotox.2019.05.011

Evaluation of a panel of in vitro methods for assessing thyroid receptor β and transthyretin transporter disrupting activitiesFinal published version, 2.24 MBLicence: Article 25fa Dutch Copyright Act

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Collet, B., Simon, E., van der Linden, S., el Abdellaoui, N., Naderman, M., Man, H. Y., Middelhof, I., van der Burg, B., Besselink, H., & Brouwer, A. (2020). Evaluation of a panel of in vitro methods for assessing thyroid receptor β and transthyretin transporter disrupting activities. Reproductive Toxicology, 96, 432-444. https://doi.org/10.1016/j.reprotox.2019.05.011

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Evaluation of a panel of in vitro methods for assessing thyroid receptor β and transthyretin transporter disrupting activities

Abstract

Funding

Keywords

UN SDGs

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