Tissue-specific effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on the activity of 5′-deiodinases I and II in rats

Abstract

Thyroid hormones play a complex role in the toxicity of polychlorinated dibenzo- p-dioxins and furans and related compounds. We investigated the toxicological significance of 5′-deiodinases I and II (5′-DI and 5′-DII) in the altered thyroid hormone status of TCDD-treated rats. Time courses and dose responses were determined for serum thyroxine (T4) and triiodothyronine (T3) levels, for 5′-DI activity in thyroid gland, liver and kidney, and for 5′-DII activity in brown adipose tissue (BAT). TCDD-treatment resulted in prompt and dose-dependent decrease in circulating T4 followed by a decrease in liver 5′-DI activity 1–2 days later and an apparent increase in BAT 5′-DII activity. Changes in liver 5′-DI and BAT 5′-DII activity were secondary to decreased T4 levels. Thyroid and kidney 5′-DI activities as well as circulating T3 levels were not affected. The results suggest that altered 5′-DI or 5′-DII activities do not significantly influence the circulating levels of T4 or T3 in TCDD-treated rats.