Gender differences exist in the incidence of cardiovascular disease and the response to major cardiovascular drugs. Women typically develop heart disease later than men and this has been attributed to the protective actions of female sex hormones, in particular, estrogen. However, there are exceptions that are yet to be understood. For instance, diabetic women are at greater risk of developing heart failure than men in response to a cardiac insult. This project will explore the importance of the estrogen receptor ERα-PI3K interaction in female and male hearts utilising mice with cardiac-specific ERα deletion, and will characterise the phenotype of ERα knockout mouse under basal conditions and in response to pressure overload.