2,3,7,8-Tetrachlorodibenzo-p-dioxin as an antiestrogen: effect on rat uterine peroxidase activity.
Treatment of 25-day-old female Sprague-Dawley rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly lowered constitutive uterine peroxidase activity and decreased uterine wet weights in a dose-response fashion. In cotreatment studies with 17 beta-estradiol, 2,3,7,8-TCDD antagonized the increase in uterine peroxidase activity and uterine wet weights, and these effects persisted for up to 156 hr. In the rat uterus, the antiestrogenic affects of two potent Ah receptor agonists, 2,3,7,8-TCDD and 2,3,4,7,8-pentachlorodibenzofuran, were comparable at a dose of 80 micrograms/kg, whereas the weaker Ah receptor agonist, 1,2,4,7,8-pentachlorodibenzo-p-dioxin, was relatively inactive at this dose. These results show that 2,3,7,8-TCDD antagonizes a well-characterized estrogen-induced response (uterine peroxidase activity), and the structure-activity data suggest that the Ah receptor is involved in mediating the antiestrogenic responses in target cells/organs.
Astroff
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B
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843.
Safe
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S
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000502:physiology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology*
D001572:Benzofurans; D004147:Dioxins; D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C051452:1,2,3,7,8-pentachlorodibenzo-p-dioxin; D004958:Estradiol; D009195:Peroxidase; C038890:2,3,4,7,8-pentachlorodibenzofuran