Superfund Research Program

Thyroid Metabolism Disruption Key in Toxicant-Induced Developmental Impairment

Project Leader: Heather M. Stapleton
Co-Investigator: P. Lee Ferguson
Grant Number: P42ES010356
Funding Period: 2011-2017

Project-Specific Links

Final Progress Reports

Year:   2016 

This project’s role in the Duke Superfund Research Center is to investigate the effects of halogenated phenolic compounds (HPCs) on development and thyroid regulation using both in vitro and in vivo models. This research group, and many others, uses the zebrafish as a model to examine development effects; however, it’s important that potential differences between zebrafish and humans be examined and considered. To this effect researchers recently developed radio-ligand binding assays to investigate the ability of HPCs to bind to and displace the endogenous thyroid hormone (T3), from both human and zebrafish thyroid nuclear receptor beta (THRB). Findings demonstrate the binding capacity of T3 to THRB is nearly identical in human and zebrafish. Furthermore, most HPCs tested did bind to THRB to a similar degree in both human and zebrafish, with only very minor differences noted. In fact, the binding affinities were highly correlated between human and zebrafish, helping to justify the use of the zebrafish to examine thyroid endpoints. Of all the HPCs tested to date, the metabolites of the flame retardants polybrominated diphenyl ethers (OH-BDEs), appear to be the most active in displacing T3 from the nuclear receptor. This is concerning given the high exposure to PBDEs in the general US population, and particularly children who have higher exposures than adults. More research is needed to understand the developmental pathways affected by displacement of T3 by these PBDE metabolites.