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Changes in thyroid hormones and thyroxine glucuronidation in hamsters compared with rats following treatment with
Abstract:
In rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, serum thyroxine (T4) is depressed. Since hamsters are relatively insensitive to TCDD-induced lethality, the effects of TCDD on several parameters of thyroid status were measured in hamsters as a comparison with the more sensitive rat. At 7 days after ip injection of TCDD, there was a dose-dependent increase in serum 3,5,3'-triiodothyronine (T3) and T4 in hamsters to a maximum level 200% of control; the ED50 was approximately 10 micrograms/kg. Hamsters receiving 100 micrograms/kg lost up to 4% of their body weight but began to recover after about 3 weeks. Serum T4 in these animals was elevated compared to pair-fed and ad libitum controls throughout the 53-day experiment, although it also began to recover after Day 21. This was in direct contrast to the marked reduction of T4 in rats exposed to lower doses of TCDD. T3 was significantly higher in TCDD-treated hamsters than in pair-fed controls on Days 2-7, and TSH was also elevated on Days 2-21. Reverse T3, like T4, was increased by TCDD in hamsters whereas it was decreased in rats. Hepatic microsomal UDP-glucuronosyltransferase (GT) activity was measured using T4 as substrate (T4-GT). On a whole liver basis, T4-GT was induced by TCDD by the same proportion in both rats and hamsters (170-180% of controls) although absolute activities in rats were 3- to 4-fold higher than in hamsters. This similarity in T4-GT inducibility by TCDD suggests that there are likely mechanisms in addition to T4-GT induction which account for the species-specific alterations in T4. Thus, while the response of thyroid hormones to TCDD differed qualitatively, effective doses in hamsters were higher than in rats, suggesting that these changes, although secondary, may correlate more directly with toxicity than does enzyme induction (whose ED50s are similar in both species). An understanding of the mechanism of this species difference may be helpful in unravelling the primary mechanisms of TCDD toxicity.