Scientific Publications by FDA Staff

Toxicol Sci 2013 Mar;132(1):75-86

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model.

Fisher JW, Gilbert M, Crofton K, Zoeller TR, McLanahan ED, Lumen A, Li S

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model parameters, were used as a technique to evaluate HPT axis adaptations to dietary iodide intake in euthyroid (4.1 -39 microg iodide/d) and iodide deficient (0.31 and 1.2 microg iodide /d) conditions. Iodide deficient conditions in both the dam and pup were described with increased blood flow to the thyroid gland, TSH-mediated increase in thyroidal uptake of iodide and binding of iodide in the thyroid gland (organification), and in general, reduced thyroid hormone production and metabolism. Alterations in thyroxine (T4) homeostasis were more apparent than for triiodothyronine (T3). Model predicted average daily area-under-the-serum-concentration-curve (AUC, nM*day) values for T4 at steady-state in the dam and pup decreased by 14-15% for the 1.2 microg iodide /d iodide deficient diet and 42 to 52% for the 0.31 microg iodide /d iodide deficient diet. In rat pups that were iodide deficient during gestation and lactation, these decreases in serum T4 levels were associated with declines in thyroid hormone in the fetal brain and a suppression of synaptic responses in the hippocampal region of the brain of the adult offspring (Gilbert et al., 2012).