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Updated: Mar 18, 2026
Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
In vitro assessment of thyroid hormone receptor activity of four organophosphate esters
Xiaomin Ren1, Linying Cao1, Yu Yang1
1State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Abstract:
Previous animal experiments have implied that organophosphate esters (OPEs) have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone (TH) nuclear receptor (TR) using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TRβ, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRβ, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR.
Insights
Organophosphate esters (OPEs) may disrupt the thyroid endocrine system. This study found OPEs activate the thyroid hormone receptor (TR), with TDCPP showing the most potent agonistic activity in vitro.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Molecular Biology
Background:
- Organophosphate esters (OPEs) are suspected endocrine disruptors.
- Previous studies suggest OPEs interfere with the thyroid endocrine system.
- The precise toxicological mechanisms remain largely unknown.
Purpose of the Study:
- To investigate the in vitro activity of four OPEs on the thyroid hormone receptor (TR).
- To elucidate the toxicological mechanisms of OPEs related to TR interaction.
- To evaluate the potential of OPEs to disrupt thyroid hormone signaling.
Main Methods:
- In vitro assays including TH-dependent cell proliferation and luciferase reporter gene assays.
- Characterization of OPEs' activity against the TR.
- Molecular docking simulations to assess ligand binding to TRβ.
Main Results:
- Tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) induced cell proliferation, unlike other OPEs.
- All four tested OPEs exhibited agonistic activity towards TRβ, with TDCPP being the most potent.
- Molecular docking confirmed OPEs binding to the TRβ ligand pocket, with TDCPP showing higher affinity.
Conclusions:
- OPEs may disrupt the thyroid endocrine system through activation of the TR.
- TDCPP demonstrates significant TRβ agonistic activity and binding affinity.
- These findings highlight a potential mechanism for OPE-induced thyroid disruption.
