The effect of 6-nitro-1,3,8-trichlorodibenzofuran as a partial estrogen in the female rat uterus.
Administration of 6-nitro-1,3,8-trichlorodibenzofuran (6-NCDF) caused a dose- and time-dependent increase in uterine wet weight and cytosolic and nuclear estrogen receptor (ER) and progesterone receptor (PR) levels in immature female Sprague-Dawley rats. These estrogenic effects persisted for up to 96 or 144 hr after initial administration of 6-NCDF and could be observed at a dose as low as 2 mumol/kg. In contrast, 6-NCDF (25 mumol/kg) did not increase rat uterine peroxidase activity or epidermal growth factor (EGF) receptor binding activity. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), which exhibits a broad spectrum of antiestrogenic effects in the female rat uterus, inhibited the 17 beta-estradiol-induced increase in uterine wet weights, cytosolic and nuclear ER and PR levels, peroxidase activity, and EGF receptor binding activity. In contrast, 2,3,7,8-TCDD inhibited the uterotropic effects caused by 6-NCDF but did not affect the 6-NCDF-induced uterine ER and PR levels. 6-NCDF is a weak inducer of hepatic microsomal ethoxyresorufin O-deethylase activity and competitively binds to the aryl hydrocarbon (Ah) receptor but not the PR or ER. Thus both 6-NCDF and 2,3,7,8-TCDD, two ligands which bind to the Ah receptor, exhibit both partial estrogenic and antiestrogenic properties and serve as useful models for delineating the complex biochemical interactions between the ER and Ah receptor signal transduction pathways.
Dickerson
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R
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843.
Howie
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L
Safe
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S
D000818:Animals; D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D001572:Benzofurans; D009574:Nitro Compounds; D000072317:Polychlorinated Dibenzodioxins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C073785:6-nitro-1,3,8-trichlorodibenzofuran; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D009195:Peroxidase; D019363:Cytochrome P-450 CYP1A1; D066246:ErbB Receptors