Thyroid status and thermogenesis in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Several key aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity resemble the effects of hypothyroidism, while in other ways the toxic responses are characteristics of hyperthyroidism. Whether thyroid dysfunction plays a role in TCDD toxicity remained unknown, however. We therefore determined the dose-related effects of TCDD treatment on plasma concentrations of L-thyroxine (T4), 3,5,3'-triiodo-L-thyronine (T3), and thyroid-stimulating hormone (TSH), and compared these changes with signs of TCDD toxicity. We also determined whether indices of functional thyroid status (and thermogenesis) were altered in response to TCDD treatment. Young adult male Sprague-Dawley rats were given single oral doses of TCDD (6.25-100 micrograms/kg) and evaluated 1 week later. Toxicity, measured by decreases in feed intake and body weight, ranged from minimal to severe. Plasma concentrations of T4 were greatly reduced at all doses tested, while T3 was increased in a dose-related fashion (up to 35%). TSH was elevated but was inversely proportional to dose. Thyroid histology was unremarkable, and TCCD treatment had little effect on the ability of rats to raise serum T4, T3, and TSH concentrations in response to acute cold stress. TCDD treatment caused a slight (8%) decrease in basal metabolic rate, yet comparable decreases were seen in pair-fed control animals. Thermogenesis, as measured by O2 consumption and colonic temperatures in rats exposed to various ambient temperatures, was only marginally affected. In summary, although thyroid hormone concentrations were markedly altered, rats given doses of TCDD sufficient to cause overt toxicity appeared to be essentially euthyroid. These results do not support proposals by other researchers that altered thyroid status is a major contributor to TCDD toxicity and/or a key response to TCDD exposure.
D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins; D051381:Rats; D011919:Rats, Inbred Strains; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood
D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; D013972:Thyrotropin