Aromatase Blockade Is Associated With Increased Mortality in Acute Illness in Male Mice

Context The increase in circulating estrogen levels with acute illness in humans is accompanied by increased aromatase expression in adipose tissue and increased peripheral aromatization of estrogens to androgens. Animal studies indicate that estrogen may be beneficial in acute illness. Objective We hypothesized that blockade of aromatase in acute illness would decrease survival. Design Prospective sham controlled. Setting Maine Medical Center Research Institute animal facility. Animals Six- to 8-week-old male black 6 mice. Intervention Mice underwent cecal ligation and puncture (CLP) to induce acute illness and were administered letrozole to block aromatase or saline. Mice undergoing sham surgery with or without letrozole served as controls. Adipose and cardiovascular tissue was harvested for preliminary evaluation of aromatase expression. Main outcome measurements Survival was the main outcome measurement. Evidence for aromatase expression in tissue samples was assessed using western blot and/or immunohistochemistry. Results With aromatase blockade, survival in CLP mice was decreased (P = 0.04). The presence of aromatase in adipose tissue was observed by western blot in CLP but not control mice. Similarly, the presence of aromatase was observed in cardiac tissue of CLP but not in control mice. Conclusions The decreased survival during sepsis with aromatase blockade suggests that this response to acute illness may be important both physiologically and clinically. The preliminary observation of aromatase expression in adipose and cardiovascular tissue during acute illness in this mouse model indicates that this model has parallels to human physiology and may be useful for further studying the aromatase response to acute illness.