Dioxins exert their actions by a specific intracellular receptor known as the Ah receptor. A disease associated with dioxin exposure is endometriosis, a painful condition briefly described as endometrial cell growth outside of the uterus. We used the human endometrial adenocarcinoma cell line, ECC-1, as a model system to study dioxin action. We examined ECC-1 cells for Ah receptor function, as determined by the induction of a cytochrome P450mediated activity, 7-ethoxycoumarin O-deethylase. ECC-1 cells exposed to 2,3,7,8-tetrachlorodibenzo-β-dioxin (TCDD) exhibited a time- and concentration-dependent increase in this enzyme activity, maximally induced by 10 nM TCDD. Using thymidine incorporation assays, an increase in DNA synthesis after 24 h exposure to 10 nM 17β-estradiol or 10 nM progesterone was observed. TCDD (10 nM) in combination with estradiol did not affect DNA synthesis, whereas TCDD ablated progestrone-induced DNA synthesis. TCDD is known to antagonize many estrogen-mediated actions in vivo and in vitro. Using a radioligand binding assay, we observed a decrease in estrogen binding cytosolic receptor in ECC-1 cells after exposure to TCDD. Our data suggest the TCDD-A/i receptor complex alters tightly regulated signal transduction pathways controlling human endometrial proliferation possibly through A/i-receptor/estrogen receptor cross-talk. Work supported by a grant from the National Institutes of Health, ES02866.
|Original language||English (US)|
|State||Published - Dec 1 1996|