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A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency
Citation:
Li, S., M. E. GILBERT, R. T. Zoeller, K. M. CROFTON, E. McLanahan, D. R. Mattie, B. C. Blount, L. Valentin-Blasini, K. Kurunthachalam, T. Kunisue, AND J. W. Fisher. A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2009.
Impact/Purpose:
A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT).
Description:
A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quantify the compensatory mechanisms that govern the relationships between serum and brain thyroid hormone (TH) concentrations in the lactating dam and the nursing neonate, 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 (ID). 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 THs, 2) negative feedback loop controlled by model-predicted brairi concentrations of T3, 3) extrathyroidal metabolism of THs by deiodinase enzymes, 4) regulation of deiodinase II in the brain, 5) serum protein binding of THs, and 6) maternal excretion of TSH and iodide via the milk. Algebraic equations were developed to describe physiological changes for the dam and nursing pups (e.g., changes in tissue volume and blood flows). The model is calibrated to predict perturbations in the HPT axis caused by ID and to ascertain the pup HPT axis tolerance to maternal ID during the nursing period. (Support: USEPA 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.)