title: Regulation of uterine hsp90alpha, hsp72 and HSF-1 transcription in B6C3F1 mice by beta-estradiol and bisphenol A: involvement of the estrogen receptor and protein kinase C.
abstract: We have previously demonstrated that bisphenol A (BPA)- and beta-estradiol (E2)-induced increases in uterine weight and heat shock protein (hsp) 90alpha and hsp72 levels are mediated through the estrogen receptor (ER). It is not, however, clear if BPA and E2 regulation of hsps is at the transcriptional or post-transcriptional level. Therefore, in this study we examined the ability of BPA and E2 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 E2 (1 microg/kg) or BPA (100 mg/kg). The role of the ER and protein kinase C (PKC) in these E2 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 E2 and BPA through a direct effect on their transcription and/or, in the case of E2, through an increase in HSF-1 mRNA. PKC is involved in the BPA-induced increases in hsp90alpha mRNA levels. We conclude that E2 and BPA regulate hsp90alpha and hsp72alpha transcription via similar and distinct pathways.
authors.affiliation: Department of Biological Sciences, George Washington University, 332 Lisner Hall, 2023 G. St. N.W., Washington, DC 20052, USA.
authors.forename: Andriana D
authors.initials: AD
authors.lastname: Papaconstantinou
authors.forename: Peter L
authors.initials: PL
authors.lastname: Goering
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Umbreit
authors.forename: Ken M
authors.initials: KM
authors.lastname: Brown
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004958:Estradiol; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D010636:Phenols; D011493:Protein Kinase C; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014157:Transcription Factors; C006780:bisphenol A; D000098826:Bisphenol A Compounds