2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) effects on hepatic microsomal steroid metabolism and serum estradiol of pregnant rats.
Experiments were conducted to evaluate the effects of administration of low, but fetotoxic quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on steroid metabolism in liver microsomes. Oral administration of 1 microgram X kg-1 X day-1 of TCDD to pregnant rats on days 7-19 of gestation reduced maternal weight gain during pregnancy. Analysis of litters on day 20 showed that fetuses from TCDD-treated dams had a 66% incidence of visceral lesions characterized by intestinal hemorrhage. Liver microsomes prepared from TCDD-treated dams on day 20 of gestation exhibited a 2- to 3-fold increase in cytochrome P-450 content which was accompanied by a shift in the absorbance optimum of the dithionite reduced-CO spectrum to 448 nm. Catechol estrogen formation activity was decreased by 50-75% in hepatic microsomes from TCDD-treated dams. In contrast 7 alpha-hydroxylation of testosterone increased nearly 4-fold, while 16 alpha- and 6 beta-hydroxylase activities were unchanged in microsomes following exposure to TCDD. Thus, the inhibition of catechol estrogen formation associated with TCDD treatment did not reflect a general decrease in microsomal steroid hydroxylase activities. Insofar as catechol estrogen formation is physiologically a major pathway for estrogen metabolism, serum concentrations of 17 beta-estradiol were measured in a second group of pregnant rats treated with TCDD on days 4-15 of gestation. Serum estradiol levels were not different between control and treated dams at this stage of pregnancy. Thus, the present study does not support a link between TCDD-mediated inhibition of catechol estrogen formation measured in vitro in liver microsomes and altered circulating estradiol levels in vivo during pregnancy.
D000818:Animals; D004147:Dioxins / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood*; D002393:Estrogens, Catechol / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D013739:Testosterone / Q000378:metabolism
D004147:Dioxins; D002393:Estrogens, Catechol; D012739:Gonadal Steroid Hormones; D000072317:Polychlorinated Dibenzodioxins; D013739:Testosterone; D004958:Estradiol