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Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs. Changes in uterine weight, epithelial cell growth, and estrogen-sensitive gene expression were assessed. TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE. Similarly, TCS increased the EE-induced stimulation of epithelial cell height following cotreatment. Cotreatment also enhanced the estrogen-induced change in gene expression, which was reversed with an ER antagonist. Furthermore, the TCS-induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay. (c) 2012 Elsevier Inc. All rights reserved.