Mechanism of the serum thyroid hormone lowering effect of perfluoro-n-decanoic acid (PFDA) in rats

The mechanism and consequences of the serum thyroid hormone lowering effect of perfluorodecanoic acid (PFDA) were examined. Thyroid and pituitary gland functions in PFDA-treated rats were assessed by measuring radioiodine uptake from the circulation and the ability of the thyroid gland to secrete thyroxine (T4) and triiodothyronine (T3) in response to thyrotropin-releasing hormone (TRH) stimulation. Serum levels of reverse triiodothyronine (rT3) were measured to test for possible conversion of T4 to a biologically inactive product and the displacement of radiolabeled T4 from rat albumin in vitro by PFDA was examined. Finally, changes in activity of the thyroid hormone-sensitive liver enzymes glycerophosphate dehydrogenase (GPD) and malic enzyme (ME) in response to PFDA were analyzed. Functional activities of the thyroid and/or pituitary glands appear to be somewhat depressed by PFDA treatment. There was no increased conversion of T4 to rT3. PFDA displaced radiolabeled T4 from rat albumin with an affinity similar to thyroxine. The activities of both GPD and ME were significantly increased in livers from PFDA-treated rats. These results suggest that decreased serum levels of thyroid hormones may be due to (1) reduced responsiveness of the thyroid and/or pituitary glands to hormonal stimulation and (2) a displacement of circulating hormones from plasma protein binding sites by PFDA. Increased activity of the liver enzymes GPD and ME does not reflect the reduction in circulating thyroid hormones and indicates that PFDA-treated rats are apparently not functionally hypothyroid at the tissue level.