The role of the estrogen receptor (ER) in the induction of abnormalities and tumors following developmental exposure to DES has also been studied using transgenic mice which overexpress ERa (MT-mER). Transgenic ER mice were treated with DES during neonatal life as described for the CD-1 mice and followed as they aged. We hypothesized that because of the abnormal expression of the ER, the reproductive tract tissues of the MT-mER mice would be more susceptible to tumors after neonatal exposure to DES. In fact, it is interesting to note that mice overexpressing ER were indeed at a higher risk of developing abnormalities including uterine adenocarcinoma in response to neonatal DES as compared to DES-treated wild type mice; at 8 months, 73% of the DES-treated MT-mER mice compared to 46 % of the DES-treated wild type mice had uterine adenocarcinoma. Further, these abnormalities occurred at an earlier age as compared to wild type DES mice . These transgenic mouse studies suggested that the level of ERa present in a tissue may be a determining factor in the development of estrogen-related tumors. However, the specific role of ER in the induction and progression of the lesions requires additional study. Other transgenic mouse models which express variant forms of ER or the ER knockout, as well as experimental models constructed with ERfi, will also aid in determining the role of the ER in the development of these reproductive lesions. Since various estrogenic compounds have been reported to bind preferentially to either ERa or ERb, these murine models will be essential in extrapolating human health risks to various environmental estrogen exposures.
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