title: The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage.
abstract: OBJECTIVE
  The aim of this study was to determine which of the estrogen receptor (ER) subtypes plays a predominant role in ameliorating hepatic damage following trauma-hemorrhage.
  
  
  METHODS
  Adult male rats were subjected to hemorrhagic shock (40 mmHg for 90 min) and resuscitation. ER-alpha agonist (PPT) or ER-beta agonist (DPN) was administered during resuscitation; rats were sacrificed 24h thereafter.
  
  
  RESULTS
  PPT or DPN decreased elevated plasma alpha-glutathione S-transferase levels; however, PPT was more effective. PPT or DPN increased hepatic heat shock protein 32 (Hsp32) mRNA/protein expressions above levels observed after trauma-hemorrhage. PPT reduced hepatic NF-kappaB and AP-1 activity and iNOS expression. Although DPN reduced hepatic NF-kappaB activity, AP-1 activity remained higher than in shams; hepatic iNOS induction remained elevated. PPT/DPN reduced nitrate/nitrite production and iNOS mRNA in Kupffer cells following trauma-hemorrhage; however, these levels in DPN-treated animals remained higher than sham.
  
  
  CONCLUSIONS
  Although both PPT and DPN decreased hepatic injury following trauma-hemorrhage, ER-alpha agonist PPT appears to be more effective in downregulating NF-kappaB and AP-1 activity, and iNOS induction. Thus, ER-alpha appears to play a predominant role in mediating the salutary effects of E2 in ameliorating hepatic damage following trauma-hemorrhage.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: László
authors.initials: L
authors.lastname: Szalay
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D005982:Glutathione Transferase / Q000097:blood / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006470:Hemorrhage / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D016328:NF-kappa B; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing); D005982:Glutathione Transferase