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.
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.
Eltom
S E
SE
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Babish
J G
JG
Ferguson
D C
DC
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007453:Iodide Peroxidase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects*; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D014284:Triiodothyronine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D007453:Iodide Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1