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Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model
U.S. Food and Drug Administration, National Center for Toxicological Research, Jefferson, USA.
Department of Biostatistics and Epidemiology, Georgia Health Sciences University, Augusta, USA.
Integrated Systems Biology Division, U.S. Environmental Protection Agency, USA.
Biology Department, University of Massachusetts, Amherst, USA.
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2013 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 132, no 1, p. 75-86Article in journal (Refereed) Published
Abstract [en]

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 µg iodide/day) and iodide-deficient (0.31 and 1.2 µg iodide/day) conditions. Iodide-deficient conditions in both the dam and the 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 (nM-day) values for T4 at steady state in the dam and pup decreased by 14-15% for the 1.2 µg iodide/day iodide-deficient diet and 42-52% for the 0.31 µg iodide/day 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. , 2013).

Place, publisher, year, edition, pages
Oxford University Press, 2013. Vol. 132, no 1, p. 75-86
Keywords [en]
BBDR, HPT axis, lactation, rat, iodide deficiency, thyroid hormones
National Category
Environmental Sciences
Research subject
Enviromental Science
Identifiers
URN: urn:nbn:se:oru:diva-83732DOI: 10.1093/toxsci/kfs336ISI: 000315434300008PubMedID: 23288054Scopus ID: 2-s2.0-84876492171OAI: oai:DiVA.org:oru-83732DiVA, id: diva2:1448045
Note

Funding Agency:

STAR USEPA, Grant Number: R832134, R8321380

FDA National Center for Toxicological Research

Available from: 2020-06-26 Created: 2020-06-26 Last updated: 2021-04-15Bibliographically approved

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Zoeller, R. Thomas

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