Depression of rat testicular 17-hydroxylase and 17,20-lyase after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), such as chloracne, hirsutism, and skin hyperpigmentation, suggest endocrine involvement, however, little is known about the effects of TCDD on steroidogenic organs. It is known that TCDD can cause decreases in testicular heme, testicular microsomal cytochrome P-450, and serum testosterone in the rat. This study was designed to examine the activities of the testicular hemoprotein microsomal cytochrome P-450-dependent enzymes, 17-hydroxylase and 17,20-lyase, following a single, oral dose of either 12.5, 25, or 50 micrograms/kg TCDD. TCDD caused dose- and time-dependent decreases in the activity of the 17-hydroxylase enzyme. Significant decreases were observed at 3, 7 and 14 days at the lowest dose of 12.5 micrograms/kg TCDD. The 17,20-lyase enzyme seemed to be less sensitive to the toxic effects of TCDD with significant decreases in enzyme activity being observed at days 3, 7 and 14 only after treatment with 50 micrograms/kg TCDD. Both microsomal cytochrome P-450 and serum testosterone levels decreased in a dose- and time-dependent manner following 12.5, 25 and 50 micrograms/kg doses of TCDD. These results indicate that decreased testosterone production following treatment with TCDD is related to decreased activities of the testicular microsomal cytochrome P-450-dependent enzymes 17-hydroxylase and 17,20-lyase.
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006418:Heme / Q000096:biosynthesis; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D013737:Testis / Q000187:drug effects* / Q000201:enzymology; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D006063:Chorionic Gonadotropin; D065607:Cytochrome P-450 Enzyme Inhibitors; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013739:Testosterone; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C022724:testosterone 7-alpha-hydroxylase, hamster; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases