Effects of beta-estradiol and bisphenol A on heat shock protein levels and localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780.

Bisphenol A (BPA) exhibits many estrogen-like effects in the rodent uterus, but not all of these can be attenuated by antiestrogens. This suggests the involvement of alternate pathways of BPA action that do not involve the estrogen receptor (ER). An examination of the in vivo effects of BPA on uterine gene expression and protein levels should contribute to an understanding of its mechanism of action. In this study we examined the dose-related effects of BPA on levels of a suite of heat shock proteins (hsps) and on the localization of hsp90 alpha, a chaperone of the ER, in uteri of ovariectomized B6C3F1 mice and compared these effects with those of beta -estradiol (E-2). The antiestrogen ICI 182,780 (ICI) was co-administered with BPA or E-2 in order to examine the potential role of the ER. BPA, although less potent than E-2, increased hsp90 alpha and grp94 to similar levels, but was much less effective than E-2 in increasing levels of hsp72. Treatment with 100 mg BPA/kg/day or 2 mug E-2/kg/day increased hsp90 alpha to 300% of control levels and altered its tissue expression pattern. In uteri of corn oil (control)-treated mice, hsp90 alpha predominantly localized in the cytoplasm and nuclei of epithelial cells. Upon treatment with BPA or E-2 there was increased intensity of staining in the stroma and myometrium, and in the epithelium hsp90 alpha was localized almost exclusively in the cytoplasm. The effects of BPA or E-2 on hsp levels and hsp90 alpha localization were attenuated by ICI. These results suggest an involvement of the ER in BPA- and E-2-induced increases in uterine levels of hsp90 alpha, grp94, and hsp72, and localization of hsp90 alpha.