The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage.
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.
Shimizu
Tomoharu
T
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yu
Huang-Ping
HP
Suzuki
Takao
T
Szalay
László
L
Hsieh
Ya-Ching
YC
Choudhry
Mashkoor A
MA
Bland
Kirby I
KI
Chaudry
Irshad H
IH
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
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