The Role of Estrogen and Receptor Agonists in Maintaining Organ Function After Trauma-Hemorrhage

Abstract

Sex is increasingly recognized as a major factor in the outcome of patients who have trauma and sepsis. Moreover, sex steroids influence chemokine/adhesion molecule expression and neutrophil accumulation. Heat shock proteins, heat shock factor 1, and peroxisome proliferator-activated receptor γ coactivator 1 are regulated by the estrogen receptors and consequently contribute to organ protection after trauma-hemorrhage. Additionally, sex steroids regulate inflammatory cytokines, leading to increased morbidity and mortality. This article deals with trauma-hemorrhage and examines the following: 1) the evidence for sex differences; 2) the mechanisms by which sex hormones affect organ protection; 3) the tissue-specific effect of sex hormone receptors; and 4) the effect of genomic and nongenomic (i.e. membrane-initiated steroid signaling) pathways of sex hormones after trauma. The available information indicates that sex steroids modulate cardiovascular responses after trauma. Thus, alteration or modulation of the prevailing hormone milieu at the time of injury seems to be a novel therapeutic option for improving outcome after injury.

Effects of 17ß-Estradiol on the Acute Necrotizing Pancreatitis after Onset in Rats

“…Studies have also shown that ER-B-mediated cardiac protection is improved by upregulation of heat shock proteins (6). Heat shock proteins are also known to regulate apoptosis (16). Besides, ER-B attenuated inflammatory response in lung and small intestine and improved hepatic function after T-H (13)(14)(15)(16).…”

“…In the last 20 years, Chaudry et al demonstrated in numerous studies that E z plays an important improving role in many organ systems after T-H and resuscitation (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The metabolic and physiologic effects of estrogen are mediated through its receptors (ER).…”

“…The metabolic and physiologic effects of estrogen are mediated through its receptors (ER). ER as isoform ER-a and ER-P are located intracellularly and act as transcription factors in modifying gene transcription after ligand binding (13)(14)(15)(16). These effects of E, are termed also genomic or nuclear effects.…”

“…These effects of E, are termed also genomic or nuclear effects. Recent studies have shown the role of ERs in Ez-mediated protection of various organ functions after T-H. ER-a reduced inflammatory response in liver and small intestine and prevented the increase in Kupfer cell cytokine production through normalized mitogen activated protein kinase activation (MAPK) after T-H and restored cytokine production of splenic macrophages, alveolar macrophages, peripheral blood mononuclear cells and improved T cells function (13)(14)(15)(16). Studies have also shown that ER-B-mediated cardiac protection is improved by upregulation of heat shock proteins (6).…”

Estradiol receptors mediate estradiol-induced inhibition of mitochondrialCa2+ efflux in rat caudate nucleus and brain stem

“…Estradiol exerts its physiological function by 2 main pathways: genomic, via the transcription of certain target genes, and nongenomic, which is independent of direct gene activation (Stormshak and Bishop, 2008;Yu and Chaudry, 2009). While genomic effects are quite well described (Chen et al, 2004;Vasudevan and Pfaff, 2008), nongenomic estradiol effects are insufficiently known and studied.…”