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DEVELOPMENTAL EXPOSURE TO A THYROID DISRUPTING CHEMICAL STIMULATES PHAGOCYTOSIS IN JUVENILE SPRAGUE-DAWLEY RATS
Citation:
Rooney, A A., R. A. Matulka, AND R W. Luebke. DEVELOPMENTAL EXPOSURE TO A THYROID DISRUPTING CHEMICAL STIMULATES PHAGOCYTOSIS IN JUVENILE SPRAGUE-DAWLEY RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Developmental Exposure to a Thyroid Disrupting Chemical Stimulates Phagocytosis in Juvenile Sprague-Dawley Rats.
AA Rooney1, R Matulka2, and R Luebke3. 1NCSU/US EPA CVM, Department of Anatomy, Physiological Sciences and Radiology, Raleigh, NC;2UNC Department of Toxicology, Chapel Hill, NC 3US EPA/NHEERL, RTP, NC.
During development, exposure to xenobiotics that disrupt the thyroid-axis may adversely impact growth and reproduction through reduced thyroid hormone (TH) concentrations. The regulatory role of THs within the immune system suggests immune function may also be negatively effected. In a previous study we observed increased phagocytic activity of peritoneal macrophages from 7-week-old offspring of Sprague-Dawley (SD) dams exposed to the anti-thyroid drug propylthiouracil (PTU, 2.0 mg/kg/day). The current study tested phagocytic responses in offspring of dams exposed to 0.02, 0.2 or 2.0 mg PTU/kg/day from gestational day 10 through post-natal day (PND) 23. Serum triidothyronine (T3) and thyroxine (T4) were measured by RIA on PNDs 14, 21, 35, 49 and 101, while peritoneal macrophage phagocytosis was measured during the time frame that offspring recover from a hypothyroid to an euthyroid state?PNDs 21, 35 and 49?to examine the relationship between phagocytic responses and circulating THs. On PND 14, mid dose offspring had lower T4 and high dose offspring had lower THs. Reduced T4 persisted in high dose offspring through PND 21 (females) and PND 49 (males). Also in high dose offspring, an increased percentage of macrophages phagocytized latex beads on PNDs 35 and 49; however, phagocytic activity was not correlated to serum THs. These results demonstrate that only developmental exposure to high doses of PTU (sufficient to cause cretinism and severely retard growth) were associated with increased phagocytic response, and that increase was only observed in rats greater than 3 weeks of age. The high doses of PTU necessary to alter phagocytosis and the lack of a clear relationship between serum THs and phagocytosis indicate that phagocytic response of peritoneal macrophages is not a sensitive indicator of developmental hypothyroidism. (This abstract does not reflect EPA policy and was supported in part by the NCSU/EPA Cooperative Training Agreement CT826512010).