Chang, Shu-Ching2009-09-092009-09-092009-07https://hdl.handle.net/11299/53380University of Minnesota Ph.D. dissertation. July 2009. Major: Toxicology. Advisor: Michael J. Murphy. 1 computer file (PDF); x, 281 pages.Perfluorooctanesulfonate (PFOS) is an environmentally stable and accumulative compound that has been found to be distributed worldwide in humans and wildlife. Although PFOS exposure has been associated with hypothyroxinemia without a compensatory elevation of thyrotropin (TSH) in the laboratory studies; human biomonitoring studies did not report any association between serum PFOS concentrations and serum thyroid hormones either. Because thyroid hormones have numerous important roles in growth and brain developments, the differences between human and laboratory rat thyroid hormone data in the presence of PFOS raise the questions of whether PFOS interferes with the thyroid homeostasis as well as whether laboratory rats serve as an appropriate model to study thyroid biology. This thesis investigated the effect of PFOS on thyroid hormone status in rats. Rats receiving PFOS appeared to maintain a euthyroid state despite significant reductions in serum total thyroid hormones and enhanced thyroid hormone turnover, likely due to competition for binding sites between PFOS and thyroid hormones in rat serum that can systematically introduces a negative bias when conventional analog methods were used to determine serum free thyroxine levels. The binding competition between PFOS and thyroid hormones did not appear to interfere with the central H-P-T axis because the ability of the pituitary to respond to hypothalamic thyrotropin-releasing hormone to release TSH in response to decreased thyroid hormone production after treatment with propylthiouracil was not altered in rats by co-treatment with PFOS. PFOS administration to maternal rats during gestation and lactation has no clear adverse effect with regards to thyroid morphology, thyroid hormone status, thyroid cell proliferation, and liver gene expression in rat offspring.In conclusion, PFOS treatment does not appear to suppress the physiological thyroid hormone status in rats.en-USNagative BiasPerfluorooctanesulfonatePFOSRatsThyroid HormoneThyroid HormonesToxicologyThesis or Dissertation