Estradiol enhances and estriol inhibits the expression of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in a mouse ovarian cancer cell line.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous pollutant and promoter of carcinogenesis. This study investigated the interaction between TCDD and different estrogens in a cancer cell line (ID8) derived from mouse ovarian epithelium. TCDD-induced ethoxyresorufin-O-deethylase (EROD) activity and cytochrome P4501A1 (CYP1A1) expression in a dose- and time-dependent manner. Estrogen receptor (ER) alpha mRNAs were constitutively expressed, but ER beta and progesterone receptor (PR) mRNAs were not expressed. Induction of EROD by TCDD was completely inhibited by a alpha-naphthoflavone and phenanthroline, two aryl hydrocarbon receptor (AhR) antagonists. Progesterone and gonadotropins (FSH and LH) had no effect on the induction of EROD by TCDD. Congeners of 17beta-estradiol (E2) increased the induction of EROD activity by TCDD dose-dependently in the relative potency order: estrone (El)>E2> or = 4-hydroxyestradiol (4OHE2)> or = 2-hydroxyestradiol (2OHE2). In contrast, estriol (E3) decreased EROD activity induced by TCDD. E2 increased TCDD-induced CYP1A1 protein and mRNA whereas E3 decreased both the protein and mRNA. E2 did not alter luciferase activity induced by TCDD in cells transfected with a luciferase reporter containing dioxin response elements (DRE) or a CYP1A1 promoter. In contrast, E3 dose-dependently decreased the luciferase activity. A pure anti-estrogen (ICI 182780) inhibited the interaction between E2 and TCDD but did not block E3's effect on EROD activity. These results indicate that E2 may affect TCDD-induced CYP1A1 expression by a mechanism different from E3 in ID8 cells. It appears that the potentiation of E2 in the induction of CYP1A1 by TCDD occurs by a mechanism involving ER alpha since a specific ER antagonist blocked the potentiation. The inhibitory effect of E3 may be due to a rapid direct effect on EROD and a later suppression of CYP1A1 expression.
Son
Deok-Soo
DS
Center for Reproductive Sciences, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Roby
Katherine F
KF
Rozman
Karl K
KK
Terranova
Paul F
PF
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D004964:Estriol / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D007202:Indicators and Reagents; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D010051:Ovarian Neoplasms / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011987:Receptors, Steroid / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D004147:Dioxins; D004785:Environmental Pollutants; D007202:Indicators and Reagents; D000072317:Polychlorinated Dibenzodioxins; D011987:Receptors, Steroid; D004958:Estradiol; D004247:DNA; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1; D004964:Estriol