Toxicological Sciences 63, 173-180 (2001)
Copyright © 2001 by the Society of Toxicology
ENDOCRINE TOXICOLOGY |
Effects of ß-Estradiol and Bisphenol A on Heat Shock Protein Levels and Localization in the Mouse Uterus Are Antagonized by the Antiestrogen ICI 182,780
,1
* Department of Biological Sciences, George Washington University, Washington, D.C. 20052;
Center for Devices and Radiological Health, Food and Drug Administration, Rockville, Maryland 20857; and
Forensic Sciences Department, George Washington University, Washington, D.C. 20052
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
, a chaperone of the ER, in uteri of ovariectomized B6C3F1 mice and compared these effects with those of ß-estradiol (E2). The antiestrogen ICI 182,780 (ICI) was co-administered with BPA or E2 in order to examine the potential role of the ER. BPA, although less potent than E2, increased hsp90 and grp94 to similar levels, but was much less effective than E2 in increasing levels of hsp72. Treatment with 100 mg BPA/kg/day or 2 µg E2/kg/day increased hsp90 to 300% of control levels and altered its tissue expression pattern. In uteri of corn oil (control)-treated mice, hsp90 predominantly localized in the cytoplasm and nuclei of epithelial cells. Upon treatment with BPA or E2 there was increased intensity of staining in the stroma and myometrium, and in the epithelium hsp90 was localized almost exclusively in the cytoplasm. The effects of BPA or E2 on hsp levels and hsp90 localization were attenuated by ICI. These results suggest an involvement of the ER in BPA- and E2-induced increases in uterine levels of hsp90, grp94, and hsp72, and localization of hsp90.
Key Words: bisphenol A (BPA); ICI 182,780 (ICI); ß-estradiol (E2); estrogen receptor (ER); uterus; heat shock proteins; hsp90 localization; B6C3F1 mouse.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. D. Salazar, M. R. Miller, J. B. Barnett, and R. Schafer Evidence for a Novel Endocrine Disruptor: The Pesticide Propanil Requires the Ovaries and Steroid Synthesis to Enhance Humoral Immunity Toxicol. Sci., September 1, 2006; 93(1): 62 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nickerson, S. L. Kennedy, J. D. Johnson, and M. Fleshner Sexual dimorphism of the intracellular heat shock protein 72 response J Appl Physiol, August 1, 2006; 101(2): 566 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Jung, E.-J. Hong, K.-C. Choi, and E.-B. Jeung Novel Progestogenic Activity of Environmental Endocrine Disruptors in the Upregulation of Calbindin-D9k in an Immature Mouse Model Toxicol. Sci., January 1, 2005; 83(1): 78 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, R. Thuillier, and M. Culty Prenatal Estrogen Exposure Differentially Affects Estrogen Receptor-Associated Proteins in Rat Testis Gonocytes Biol Reprod, November 1, 2004; 71(5): 1652 - 1664. [Abstract] [Full Text] [PDF]
|
|