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

ABSTRACT

We developed a thyroid testing panel to assess endocrine disrupting chemicals (EDCs) capacities to bind either the thyroid receptor ß (TRß) or the thyroid hormones transporter transthyretin (TTR). We first stably transfected a human U2OS cell line with TRß and a luciferase reporter construct to develop the TRß CALUX® reporter gene assay to assess chemicals' potential to interact with TRß. Secondly, we combined a TTR-binding assay with the TRß CALUX (TTR-TRß 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 TRß CALUX successfully predicted 9/9 and 9/12 test compounds, respectively. The TTR-TRß 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.