2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated depression of rat testicular heme synthesis and microsomal cytochrome P-450.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces hirsutism, alopecia, and chloracne, symptoms that suggest a possible alteration of endocrine function. Therefore, the effects of TCDD on rat testicular cytochrome P-450 content were investigated. Forty-eight hours after a single, oral dose of TCDD (25 microgram/kg) testicular microsomal cytochrome P-450 levels were depressed by approximately 24%. Microsomal cytochrome P-450 continued to decrease to 62% of control levels at 4 days and remained at approximately the same levels 7 days following treatment. Testicular microsomal heme content exhibited a similar pattern after administration of TCDD. No alterations in testicular delta-aminolevulinic acid (ALA) synthase were detected. The incorporation of [14C]ALA into microsomal heme was decreased to approximately 36% of control values at 24 hr after TCDD administration. Testicular weights were not altered during the 7-day experimental period. These data suggest that TCDD depresses cytochrome P-450 levels in the rat testis through an inhibition of the synthesis of testicular heme.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology*; D006418:Heme / Q000096:biosynthesis*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D006418:Heme; D000622:Aminolevulinic Acid; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase