EXTRATHYROIDAL EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON THYROID-HORMONE TURNOVER IN MALE SPRAGUE-DAWLEY RATS

Treatment of rats with different polyhalogenated aromatic hydrocarbons strongly decreases plasma T-4, with little or no decrease in plasma T -3. The extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone turnover were studied by ip administration o f a single dose of 10 mu g TCDD/kg BW or vehicle (corn oil) to euthyro id (Eu) rats, thyroidectomized (Tx) rats, and Tx rats infused with 1 m u g T-4 (Tx+T-4) or 0.4 mu g T-3 (Tx+T-3)/100 g BW.day by osmotic mini pumps. Tx rats showed decreased plasma T-4 and T-3 and increased plasm a TSH levels, decreased hepatic type I deiodinase (D1) and malic enzym e activities, and increased brain type II deiodinase (D2) activities. All parameters were largely restored to Eu levels in Tx+T-4 rats and, except for plasma T-4 and brain D2 activity, in Tx+T-3 rats, validatin g the thyroid hormone-replaced Tx rats as models to study the peripher al effects of TCDD. Three days after TCDD administration, plasma T-4 a nd free T-4 levels were significantly reduced in Eu and Tx+T-4 rats, a nd plasma T-3 was significantly reduced in Tx+T-3, but not in Eu or Tx +T-4 rats. Plasma TSH was not affected by TCDD in any group. Hepatic T -4 UDP-glucuronyltransferase (UGT) activity was induced approximately 5-fold by TCDD, whereas T-3 UGT activity was only increased by about 2 0% (P = NS) in the different groups. TCDD produced an insignificant de crease in liver D1 activity in Tx rats and an insignificant increase i n brain D2 activity in Tx rats and hormone-replaced Tx rats. Hepatic m alic enzyme activity was significantly increased by TCDD in all groups , except Tx rats. These results strongly suggest that the thyroid horm one-decreasing effects of TCDD are predominantly extrathyroidal and me diated by the marked induction of hepatic T-4 UGT activity.