6 research outputs found
Sex Hormones and Gender Effects following Trauma-Hemorrhage
Trauma is the leading cause of death in the industrialized world between the ages of one and 40. A number of risk factors
including age and gender have been implicated in this regard. It is therefore not surprising that the majority of trauma victims
are young males. Their mortality rate following trauma is not only higher compared to females, but they are also more
prone to subsequent sepsis. Age and gender are therefore important factors in the prevalence of traumatic injury as well
as in susceptibility to subsequent septic complications
Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers
17β-Estradiol normalizes Toll receptor 4, mitogen activated protein kinases and inflammatory response in epidermal keratinocytes following trauma-hemorrhage
Lack of Effect of Metformin on Mammary Carcinogenesis in Nondiabetic Rat and Mouse Models
Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention
Estradiol’s Salutary Effects on Keratinocytes Following Trauma-Hemorrhage Are Mediated by Estrogen Receptor (ER)-α and ER-β
Although administration of 17β-estradiol (estrogen) following trauma-hemorrhage attenuates the elevation of cytokine production and mitogen-activated protein kinase (MAPK) activation in epidermal keratinocytes, whether the salutary effects of estrogen are mediated by estrogen receptor (ER)-α or ER-β is not known. To determine which estrogen receptor is the mediator, we subjected C3H/HeN male mice to trauma-hemorrhage (2-cm midline laparotomy and bleeding of the animals to a mean blood pressure of 35 mmHg and maintaining that pressure for 90 min) followed by resuscitation with Ringer’s lactate (four times the shed blood volume). At the middle of resuscitation we subcutaneously injected ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), estrogen (50 μg/kg), or ER antagonist ICI 182,780 (150 μg/kg). Two hours after resuscitation, we isolated keratinocytes, stimulated them with lipopolysaccharide for 24 h (5 μg/mL for maximum cytokine production), and measured the production of interleukin (IL)-6, IL-10, IL-12, and TNF-α and the activation of MAPK. Keratinocyte cytokine production markedly increased and MAPK activation occurred following trauma-hemorrhage but were normalized by administration of estrogen, PPT, and DPN. PPT and DPN administration were equally effective in normalizing the inflammatory response of keratinocytes, indicating that both ER-α and ER-β mediate the salutary effects of estrogen on keratinocytes after trauma-hemorrhage