2005 Progress Report: Low-Dose Effects of Thyroid Toxicants on NeurodevelopmentEPA Grant Number: R832137
Title: Low-Dose Effects of Thyroid Toxicants on Neurodevelopment
Investigators: Zoeller, R. Thomas
Institution: University of Massachusetts - Amherst
EPA Project Officer: Hahn, Intaek
Project Period: December 1, 2004 through November 30, 2008
Project Period Covered by this Report: December 1, 2004 through November 30, 2005
Project Amount: $738,971
RFA: Development and Characterization of Biological Systems for Studying Low Dose Effects of Endocrine Disrupting Chemicals (2004) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Endocrine Disruptors , Health , Safer Chemicals , Health Effects
The objectives of this research project are to test the hypothesis that thyroid hormone produces nonlinear, dose-dependent effects on endpoints within the developing brain, heart, and liver and to determine if some endpoints are more sensitive than others to thyroid hormone. In addition, we propose that thyroid toxicants disrupting the hypothalamic pituitary thyroid (HPT) axis by different mechanisms will produce different dose-response curves on these endpoints. Finally, a principle mechanism shaping the dose-response curve to thyroid hormone or by extension, thyroid disrupters, are changes in tissue metabolism of thyroid hormone in response to perturbations in the HPT axis.
We have made significant progress toward the stated objectives, especially the formation of a cooperative agreement with the U.S. Environmental Protection Agency and with investigators at the University of Georgia. We have identified thyroxine-binding globulin (TBG) in rat pup serum at high levels and have validated a quantitative real time-polymerase chain reaction approach to study the regulation of TBG gene expression in liver. We also have validated the tissue radioimmunoassay for T4 and are developing a new T3 assay for use in these experiments. Two of the three animal studies now are completed with tissues collected and being prepared for analysis. The rate of spending is running a little lower than expected but is expected to be compensated over the ensuing funding periods.
We will continue evaluating endpoints of thyroid hormone action affected by low-dose exposure to the three chosen toxicants. Our plan is to pursue this work exactly as described in the original proposal. We fully expect to have this fully completed by this time next year. In addition, we will perform the polybrominated diphenyl ether experiment, as described in the original application, during the summer of 2006. We will begin to process this tissue during the upcoming FY.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
|Other project views:||All 36 publications||23 publications in selected types||All 21 journal articles|
||Sharlin DS, Bansal R, Zoeller RT. Polychlorinated biphenyls exert selective effects on cellular composition of white matter in a manner inconsistent with thyroid hormone insufficiency. Endocrinology 2006;147(2):846-858.||