THE INTERACTION OF L-TRIIODOTHYRONINE AND 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN ON AH-RECEPTOR-MEDIATED HEPATIC PHASE-I AND PHASE-II ENZYMES AND IODOTHYRONINE 5'-DEIODINASE IN THYROIDECTOMIZED RATS

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 t.-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.