Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats.
Administration of a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 20 or 80 micrograms/kg) resulted in significantly decreased hepatic and uterine estrogen receptor (ER) levels in 25-day-old female Long-Evans rats. By contrast, estradiol (5 and 15 micrograms/kg) administration increased hepatic and uterine ER levels, while a combination of 2,3,7,8-TCDD plus estradiol resulted in uterine and hepatic ER levels which were similar or lower than those observed after treatment with only 2,3,7,8-TCDD. In addition, 2,3,7,8-TCDD significantly decreased the effects of estradiol on uterine wet weight increase. Competitive binding studies showed that estradiol did not bind to the aryl hydrocarbon (Ah) receptor and that 2,3,7,8-TCDD did not bind to the ER. The effects of structure on the activity of polychlorinated dibenzo-p-dioxin congeners on their activity to down-regulate hepatic and uterine ER levels were determined by using 2,3,7,8-TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,3,7,8-TCDD, and 1,2,4,7,8-PeCDD. Both 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD exhibit high affinities for the Ah receptor and at dose levels of 80 micrograms/kg the hepatic ER levels were decreased 42 and 41%, respectively, and uterine ER levels were decreased 53 and 49%, respectively. 1,3,7,8-TCDD and 1,2,4,7,8-PeCDD bind less avidly to the Ah receptor and at dose levels of 400 micrograms/kg these compounds decreased hepatic ER levels 36 and 40%, respectively, and uterine ER levels 21 and 24%, respectively. These results support a role for the Ah receptor in the down-regulation of uterine and hepatic ER levels in the female rat by 2,3,7,8-TCDD and this effect may be associated with the decrease in spontaneous mammary and uterine tumors observed in female rats treated with 2,3,7,8-TCDD.
D000818:Animals; D001667:Binding, Competitive; D002499:Centrifugation, Density Gradient; D004147:Dioxins / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011960:Receptors, Estrogen; C051452:1,2,3,7,8-pentachlorodibenzo-p-dioxin; D004958:Estradiol