Estrogenic hormone modulation abrogates changes in red blood cell deformability and neutrophil activation in trauma hemorrhagic shock

J Trauma. 2010 Jan;68(1):35-41. doi: 10.1097/TA.0b013e3181bbbddb.


Background: Decreased red blood cell (RBC) deformability and activation of neutrophils (polymorphonuclear leukocytes [PMN]) after trauma-hemorrhagic shock (T/HS) have been implicated in the development of multiple organ dysfunction. Experimentally, female animals seemed to be protected from the effects of T/HS, at least in part, because of elevated estrogen levels. Thus, we examined the relative role of estrogen receptor (ER)-alpha and -beta in this protective response.

Methods: To accomplish this goal, RBC deformability and neutrophil respiratory burst activity were measured in several groups of hormonally intact or ovariectomized (OVX) female rats subjected to T/HS (laparotomy plus hemorrhage to an MAP of 30 mm Hg to 35 mm Hg for 90 minutes) or trauma-sham shock (T/SS) and 3 hours of reperfusion. These groups included rats receiving vehicle, estradiol, or either an ER-alpha agonist or an ER-beta agonist administered at the end of the shock period just before volume resuscitation.

Results: RBC deformability and neutrophil activation were similar among all the T/SS groups and were not different from that observed in the non-OVX female rats subjected to T/HS. In contrast, RBC deformability was reduced and neutrophil activation was increased in the OVX, T/HS female rats as compared with the T/SS groups or the non-OVX, T/HS rats. The administration of estrogen to the T/HS, OVX rats returned RBC and neutrophil function to normal. Both the ER-alpha and -beta agonist partially, but not completely, protected the OVX rats from T/HS-induced loss of RBC deformability, whereas only the ER-beta agonist prevented the increase in neutrophil activation.

Conclusions: The protective effects of estrogen on T/HS-induced RBC deformability are mediated, at least in part, via activation of both ER-alpha and -beta, whereas ER-beta activation is involved in limiting T/HS-induced neutrophil activation.

MeSH terms

  • Animals
  • Erythrocyte Deformability*
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / physiology*
  • Estrogen Receptor beta / agonists
  • Estrogen Receptor beta / physiology*
  • Female
  • Neutrophil Activation / drug effects
  • Neutrophils / metabolism
  • Nitriles / pharmacology
  • Ovariectomy
  • Phenols
  • Propionates / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Burst
  • Shock, Hemorrhagic / blood*
  • Shock, Hemorrhagic / physiopathology
  • Shock, Traumatic / blood*
  • Shock, Traumatic / physiopathology


  • 2,3-bis(4-hydroxyphenyl)-propionitrile
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Nitriles
  • Phenols
  • Propionates
  • Pyrazoles
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol