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Updated: Jun 13, 2026

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Hormone activity of hydroxylated polybrominated diphenyl ethers on human thyroid receptor-beta: in vitro and in
1Key Laboratory of Industrial Ecology and Environmental Engineering, School of Environmental Science and Technology, Dalian University of Technology, Dalian, China.
Background:
Hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disrupt thyroid hormone status because of their structural similarity to thyroid hormone. However, the molecular mechanisms of interactions with thyroid hormone receptors (TRs) are not fully understood.
Objectives:
We investigated the interactions between HO-PBDEs and TRbeta to identify critical structural features and physicochemical properties of HO-PBDEs related to their hormone activity, and to develop quantitative structure-activity relationship (QSAR) models for the thyroid hormone activity of HO-PBDEs.
Methods:
We used the recombinant two-hybrid yeast assay to determine the hormone activities to TRbeta and molecular docking to model the ligand-receptor interaction in the binding site. Based on the mechanism of action, molecular structural descriptors were computed, selected, and employed to characterize the interactions, and finally a QSAR model was constructed. The applicability domain (AD) of the model was assessed by Williams plot.
Results:
The 18 HO-PBDEs tested exhibited significantly higher thyroid hormone activities than did PBDEs (p < 0.05). Hydrogen bonding was the characteristic interaction between HO-PBDE molecules and TRbeta, and aromaticity had a negative effect on the thyroid hormone activity of HO-PBDEs. The developed QSAR model had good robustness, predictive ability, and mechanism interpretability.
Conclusions:
Hydrogen bonding and electrostatic interactions between HO-PBDEs and TRbeta are important factors governing thyroid hormone activities.
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