Sex‐based differences in the response of the heart to stimuli

The mouse heart responds to a wide variety of pathologic and physiologic stimuli in a sexually dimorphic manner. Generally, female mice do not exhibit as much pathology as males in response to acquired or genetic heart disease and less cardiac atrophy in response to cancer. Female mice run more than males on a voluntary cage wheel and have a greater hypertrophic response per kilometer run. We have explored the basis for these differences using a variety of approaches. To test the role of estrogen in both pathologic and physiologic hypertrophy, we have studied aromatase null mice. As opposed to surgical gonadectomies where there is residual estrogen, aromatase null mice have no estrogen. In contrast to wild‐type (WT) females, aromatase null female mice run on a voluntary wheel less; and they are now equivalent to male WT or aromatase nulls. Female aromatase nulls have increased hypertrophy in response to isoproterenol and their response is equivalent to WT and aromatase null males. However, unlike WT and aromatase null males, females do not show an induction of genes normally associated with pathologic hypertrophy. We have also begun to investigate the effect of soy phytoestrogens on laboratory mice since their typical diet is soy‐based and have found that they have profound effects in a sex‐specific manner on cardiac gene expression, exercise and genetic heart disease. This research was supported by NIHR01 HL50560.