Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism

Abstract

The potential toxicity of perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, is of great concern. The present study examines the ability of PFOS to disturb thyroid function and the possible mechanisms involved in PFOS-induced thyroid hormone alteration. Male Sprague-Dawley rats were exposed to 1.7, 5.0, and 15.0 mg/L of PFOS in drinking water for 91 consecutive days. Serum was collected for analysis of total and free thyroxine (T4), total triiodothyronine (T3), and thyrotrophin (TSH). Thyroid and liver were removed for the measurement of endpoints closely related to thyroid hormone biosynthesis and metabolism following PFOS exposure. Determined endpoints were the messenger RNA (mRNA) levels for two isoforms of uridine diphosphoglucuronosyl transferases (UGT1A6 and UGT1A1) and type 1 deiodinase (DIO1) in liver, sodium iodide symporter (NIS), TSH receptor (TSHR), and DIO1 in thyroid as well as the activity of thyroid peroxidase (TPO). Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed. Hepatic UGTIA1, but not UGT1A6, mRNA was up-regulated at 5.0 and 15.0 mg/L of PFOS. Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats.

Environmental Thyroid Disruptors and Human Endocrine Health

“…A similar mechanism for PFOS has been hypothesized (Chang et al, 2008). A recent study of the mechanisms involved in PFOS-induced hypothyroxinemia in rats has indicated that increased conjugation of T4 in the liver, catalyzed by the hepatic enzyme UDP-GT 1A1, and increased thyroidal conversion of T4 to T3 by type 1 deiodinase may be partly responsible for the effects (Yu et al, 2009). Taken together, these findings suggest that the PFAA actions on the thyroid system are multiple and complex.…”

Perfluorooctane sulfonic acid exposure increases cadmium toxicity in early life stage of zebrafish, Danio rerio

“…Lau et al [27] and Thibodeaux et al [28] reported reductions in total or free serum T4 in PFOStreated rats and mice. Yu et al [29] also showed the increase in serum T3 in PFOS-treated rats. Approximately 80% of serum T3 is the product of T4 conversion by 5 0 -deiodination in peripheral tissues, and the remaining 20% is secreted by thyroid gland [30].…”

Structure–activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor

“…Numerous studies on the molecular mechanisms of PFCs' toxicities were carried out through the levels of THs transport and metabolism (Chen and Guo 2009;Yu et al 2009a). However, the study of PFCs' effect on TR pathway was still very limited.…”