Effect of thyroid hormones on liver microsomal enzyme induction in rats exposed to 2,3,7,8,-tetrachlorodibenzo-p-dioxin.
The effect of thyroidectomy and thyroid hormone replacement therapy on liver microsomal enzyme induction was studied in 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats (100 micrograms/kg). Treatment of non-thyroidectomized rats with TCDD had no effect on the concentration of liver microsomal cytochrome b5. In contrast, cytochrome b5 content was increased by TCDD treatment of thyroidectomized rats, regardless of replacement therapy with either T3 or T4. TCDD treatment increased the concentration of cytochrome P-450 (2-3-fold) and the activities of benzo[a]pyrene hydroxylase (4-7-fold), ethoxyresorufin O-de-ethylase (50-70-fold) and UDP-glucuronosyltransferase (5-7-fold) in non-thyroidectomized and thyroidectomized as well as thyroidectomized thyroid hormone treated rats; indicating the induction of these liver microsomal enzyme activities is independent of thyroid status. Because thyroid status alters the toxicity of TCDD but does not alter the ability of TCDD to induce microsomal enzymes, it appears that TCDD toxicity may not be directly related to microsomal enzyme induction.
D000284:Administration, Oral; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D003573:Cytochrome b Group / Q000096:biosynthesis; D015786:Cytochromes b5; D004147:Dioxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood / Q000502:physiology*; D014284:Triiodothyronine / Q000097:blood / Q000502:physiology*
D003573:Cytochrome b Group; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014284:Triiodothyronine; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001579:Benzopyrene Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D009251:NADPH-Ferrihemoprotein Reductase; D013974:Thyroxine