Interactive effects of estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic cytochrome P-450 and mouse uterus.
Weanling C57B/6 female mice treated with 6 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 3 times a week for one month (total dose 72 micrograms/kg) were observed to have greatly reduced relative uterine weights and histopathological changes in the uterus. Weanling CD-1 female mice were then treated with estradiol (E2) subcutaneously daily for 2 weeks. Half the mice also received 10 micrograms/kg TCDD in corn oil: acetone (9:1) by gavage 4 times during the second week. Control mice received either no E2 or no TCDD. Mice were killed on day 15 and autopsied. Relative uterine weights increased with increasing E2 doses; however, TCDD decreased this effect of E2 markedly. Liver microsomes from these animals showed that cytochrome P1-450 and P3-450 and, aryl hydrocarbon hydroxylase (AHH) induction by TCDD were independent of E2 dosage. Epoxide hydrolase was induced in TCDD treated animals. Gels showed an E2 dose dependent decrease in a protein migrating near epoxide hydrolase and 'P-450a' in animals receiving both E2 and TCDD. These results suggest that: E2 may act at the TCDD receptor; the TCDD receptor may be related to the estrogen receptor; the anti-estrogenic effects of TCDD are possibly independent of the Ah locus and AHH induction, and in TCDD-treated mice a protein migrating near epoxide hydrolase and 'P-450a' may be controlled by estrogen levels.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases