You are here:
A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency
Citation:
Fisher, J. W., M. E. GILBERT, R. T. Zoeller, K. M. CROFTON, E. McLanahan, D. R. Mattie, AND S. Li. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT).
Description:
A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fetus quantify the compensatory mechanisms that govern the relationships between serum and brain thyroid hormone (TH) concentrations in the pregnant dam and fetus, recognizing that these relationships may be affected by the mechanism of toxicity of different compounds. Initially, the model will be used to delineate perturbations in the HPT axis caused by inadequate dietary iodide. Later, environmental toxicants that alter HPT axis homeostasis will be examined. The current model uses the McLanahan et al. (2009) BBDR-HPT axis model for the adult rat as a foundation, but includes several new features: 1) formation rates of thyroid hormones, 2) negative feedback loop controlled by model-predicted brain concentrations of T3 3) extrathyroidal metabolism of thyroid hormones by deiodinase enzymes, 4) regulation of deiodinase II activity in the brain , and 5) serum protein binding of thyroid hormones. Algebraic equations were developed to describe physiologic changes in the fetus ( growth of the fetus, cardiac output, plasma volume, umbilical venous and arterial blood flow, growth ofthe thyroid gland and brain), and the dam (growth the placenta, uterus, liver, brain, thyroid gland, deiodinase II and III activity in the placenta, plasma volume, cardiac output and blood flow to the uterus and placenta). Data sets were derived from the literature and from ongoing collaborative research Calibration of the BBDR-HPT axis model will predict perturbations in the HPT axis caused by iodide deficiency, and ascertain the feted HPT axis tolerance to maternal iodide deficiency before and after the HPT axis is functional in the fetus (GD 17.5). (Support: US EPA STAR Cooperative Agreement R832134 and AFRL through the Henry Jackson Foundation for the Advancement of Military Medicine Contract 185137. This abstract does not necessarily reflect EPA policy.)