Estrogenic effects involve interactions between estrogen receptors (ERs), response elements, and nuclear proteins. It is hypothesized that interaction between ER and NF-κ B may affect the regulation of responsive genes. Electrophoretic mobility shift assay (EMSA) was performed to assess if the interaction of ERs and NF- κB affect their respective DNA-binding activities, and alkaline phosphatase assay was done to evaluate estrogenic activity. EMSA revealed that ERs inhibit DNA-binding of p50 and p65, whereas p50 did not impair ER α binding. Stimulation with estradiol inhibited DNA binding of NF-κB in ERα-transfected endometrial stromal cells (ESCs). Moreover, activation of NF-κB significantly decreased estrogen responsiveness of Ishikawa cells and ERα-transfected ESC. Our results suggest that ERs downregulate NF-κB-dependent gene activation by directly preventing DNA binding. However, NF-κB-mediated inhibition of ER-dependent gene activation may be carried out indirectly rather than through a direct inhibition of ER-DNA binding. These findings offer new insight into the specific role of ERα and could eventually help in developing therapeutics for endometriosis.
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