The interaction of l-triiodothyronine and 2,3,7,8-tetrachlorodibenzo- p-dioxin on Ah-receptor-mediated hepatic Phase I and Phase II enzymes and iodothyronine 5'-deiodinase in thyroidectomized rats

Abstract

Across all levels of l-triiodothyronine ( l.-T3) treatment, 2,3.7.8-tetrachlorodibenzo- p-dioxin (TCDD) resulted in increased hepatic cytochrome P-450-associated activities of 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O-dealkylase (EROD) and aryl hydrocarbon hydroxylase (AHH). The treatment of thyroidectomized rats with l-T3 at physiologic replacement levels in concert with TCDD produced an increase in ECOD, EROD and AHH activity above that seen with only TCDD. TCDD as well as l-T3 enhanced the activity of hepatic 1-naphthol glucuronyl transferase (NGT). In addition, the combined effect of l-T3 and TCDD resulted in similar levels of induction of NGT at both physiologic and supraphysiologic doses of l-T3. TCDD treatment resulted in elevated serum T3 levels at both physiologic and supraphysiologic levels of l-T3. One TCDD dose inhibited hepatic microsomal 3,3',5'-triiodothyronine (reverse T3) 5'-deiodinase activity by 61 % in thyroidectomized, T3-untreated rats. The inhibition of 5'-deiodinase activity was partially overcome by increasing the T3 dose.