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IODIDE DEFICIENCY, THYROID HORMONES, AND NEURODEVELOPMENT
Citation:
GILBERT, M. E., J. M. HEDGE, K. Grant, I. GITATA, D. F. LYKE, J. Fisher, R. T. ZOELLER, AND K. M. CROFTON. IODIDE DEFICIENCY, THYROID HORMONES, AND NEURODEVELOPMENT. Presented at Annual meeting of the Society of Toxicology, Baltimore, MD, March 16 - 20, 2009.
Impact/Purpose:
ABSTRACT BODY: Iodide is an essential nutrient for thyroid hormone synthesis. Severe iodide insufficiency during early development is associated with cognitive deficits. Environmental contaminants can perturb the thyroid axis and this perturbation may be more acute under conditions of marginal iodine deficiency. The present study examined the relationship between graded levels of iodide deficiency in pregnant rats on hormonal status and behavioral indices of brain function in exposed offspring. This data is being generated to inform an exposure-dose-response model for developmental disruption of thyroid hormones. Female Long Evans rats (n=60, ~ 60 days of age) were placed on diets with varying degrees of iodine deficiency for 7 wks prior to breeding. Iodine was added to a casein-based diet (25 µg/kg background levels) resulting in the following experimental groups: total 25 µg/kg (severely deficient), 75, 175, 275 (normal control diet) and 1025 µg/kg (excess). Pups were sacrificed on postnatal day (PN) 4, 14 and 21 and blood, lung, liver, heart, thyroid glands, and brain were harvested. Dams were sacrificed at weaning for hormone analysis. Behavioral assessments were performed on male and female offspring (4-5 months of age) using a sensory gating paradigm based on auditory startle, spatial learning using a Morris water maze, and associative learning using a trace fear conditioning paradigm. Thyroxine was reduced (~45%) and TSH increased (2-3-fold) in dams and pups on PN21 in the 25 µg/kg iodine group. No changes in T3 were evident. Thyroid weights were significantly increased in pups on PN21 with nonsignificant increases also evident in dams. Preliminary analyses reveal no evidence of impairment in any of the behavioral tasks in either gender. These data demonstrate dose-dependent effects of iodine deficiency on thyroid hormones during development, however no impairments in behavioral indices of cognitive function were detected. (Does not necessarily reflect EPA policy)
Description:
ABSTRACT BODY: Iodide is an essential nutrient for thyroid hormone synthesis. Severe iodide insufficiency during early development is associated with cognitive deficits. Environmental contaminants can perturb the thyroid axis and this perturbation may be more acute under conditions of marginal iodine deficiency. The present study examined the relationship between graded levels of iodide deficiency in pregnant rats on hormonal status and behavioral indices of brain function in exposed offspring. This data is being generated to inform an exposure-dose-response model for developmental disruption of thyroid hormones. Female Long Evans rats (n=60, ~ 60 days of age) were placed on diets with varying degrees of iodine deficiency for 7 wks prior to breeding. Iodine was added to a casein-based diet (25 µg/kg background levels) resulting in the following experimental groups: total 25 µg/kg (severely deficient), 75, 175, 275 (normal control diet) and 1025 µg/kg (excess). Pups were sacrificed on postnatal day (PN) 4, 14 and 21 and blood, lung, liver, heart, thyroid glands, and brain were harvested. Dams were sacrificed at weaning for hormone analysis. Behavioral assessments were performed on male and female offspring (4-5 months of age) using a sensory gating paradigm based on auditory startle, spatial learning using a Morris water maze, and associative learning using a trace fear conditioning paradigm. Thyroxine was reduced (~45%) and TSH increased (2-3-fold) in dams and pups on PN21 in the 25 µg/kg iodine group. No changes in T3 were evident. Thyroid weights were significantly increased in pups on PN21 with nonsignificant increases also evident in dams. Preliminary analyses reveal no evidence of impairment in any of the behavioral tasks in either gender. These data demonstrate dose-dependent effects of iodine deficiency on thyroid hormones during development, however no impairments in behavioral indices of cognitive function were detected. (Does not necessarily reflect EPA policy)