Tissue-specific effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the activity of 5'-deiodinases I and II in rats.
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.
Viluksela
Matti
M
Laboratory of Toxicology, National Public Health Institute, FIN-70701 Kuopio, Finland. matti.viluksela@ktl.fi
Raasmaja
Atso
A
Lebofsky
Margitta
M
Stahl
Bernhard U
BU
Rozman
Karl K
KK
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007453:Iodide Peroxidase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology; D013963:Thyroid Hormones / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D007527:Isoenzymes; D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; D007453:Iodide Peroxidase; D019363:Cytochrome P-450 CYP1A1