Regulation of uterine hsp90α, hsp72 and HSF-1 transcription in B6C3F1 mice by β-estradiol and bisphenol A: involvement of the estrogen receptor and protein kinase C

Abstract

We have previously demonstrated that bisphenol A (BPA)- and β-estradiol (E 2)-induced increases in uterine weight and heat shock protein (hsp) 90α and hsp72 levels are mediated through the estrogen receptor (ER). It is not, however, clear if BPA and E 2 regulation of hsps is at the transcriptional or post-transcriptional level. Therefore, in this study we examined the ability of BPA and E 2 to increase uterine weight and regulate transcription of these hsps and of heat shock factor (HSF)-1 in ovariectomized B6C3F1 mice at 6 or 24 h after a single subcutaneous injection of E 2 (1 μg/kg) or BPA (100 mg/kg). The role of the ER and protein kinase C (PKC) in these E 2 and BPA effects was evaluated by co-administration of the antiestrogen ICI 182,780 (5 mg/kg) or the PKC inhibitor GF 109203X (0.5 mg/kg), respectively. The results demonstrated ER involvement in uterine weight increases. Uterine hsp mRNA levels are increased by E 2 and BPA through a direct effect on their transcription and/or, in the case of E 2, through an increase in HSF-1 mRNA. PKC is involved in the BPA-induced increases in hsp90α mRNA levels. We conclude that E 2 and BPA regulate hsp90α and hsp72α transcription via similar and distinct pathways.