Developmental Toxicants: Mechanisms, Consequences, and Remediation - Project 2: Thyroid Metabolism Disruption in Toxicant-Induced Developmental Impairment

Heather Stapleton (PI) and P. Lee Ferguson (co-PI)
Funding Agency: 
NIEHS Superfund Research Program

Many halogenated, persistent, and bioaccumulative contaminants have been classified as endocrine disruptors, and in many cases these contaminants negatively impact thyroid regulation. Exposure to organochlorine pesticides, PCBs and newly-emerging contaminants such as PBDEs and triclosan, have all been shown to cause thyroid dysregulation, often by depressing circulating levels of thyroid hormones. However, the mechanisms responsible for these changes are unclear. This new mechanism-based project examines impacts on thyroid regulation from exposure to halogenated chemical contaminants using novel approaches. This project combines the use of a new high throughput in vitro assay, and uses in vivo (zebrafish-based) studies of complex systems and function, to examine chemical effects on thyroid hormone levels in tissues, thyroid hormone metabolism and expression of thyroid regulating genes, and examining their relation to larger scale effects on development and function. These studies will help to elucidate the mechanisms of thyroid toxicity and the mechanistic events that produce adverse effects on growth and development later in life.