To investigate the interference of various compounds with thyroid hormone binding proteins (THBPs) and their effect on the binding of L-thyroxine (T4) to TTR and TBG.
Approach:
THPB Assay Development: A thyroid hormone protein binding (THPB) assay was established to measure the displacement of T4 from different binding proteins, including TTR, TBG, and total serum, using size exclusion chromatography (SEC) and quantification by LC-MS.
Key Findings:
Eight test substances were evaluated for their ability to displace T4 from human TTR, TBG, and mixtures of THBPs.
The study highlights the importance of considering multiple THBPs in assessing the effects of exogenous compounds on thyroid hormone transport.
Interpretation:
The findings indicate that various compounds can interfere with T4 binding to THBPs.
Limitations:
The study primarily focuses on TTR and does not extensively evaluate other THBPs.
The extrapolation of rodent study findings to humans remains uncertain due to differences in THBP composition.
Conclusion:
The assay developed provides a method to assess the impact of environmental chemicals on thyroid hormone binding.