Cross-coupling between the oestrogen receptor and phosphoinositide 3-kinase

Gender differences in cardiovascular mortality are well documented and oestrogen replacement therapy in post-menopausal women is associated with improved outcomes from cardiovascular events. Indeed, oestrogen therapy has been shown to restore endothelial function in post-menopausal women and reduce the development of atherosclerotic lesions. Despite extensive evidence on the beneficial effect of oestrogen, relatively little is known regarding the molecular signalling mechanism(s) by which oestrogen exerts some of its vascular effects. While the nuclear function of the oestrogen receptor is clearly established, previous studies regarding the membrane and cytoplasmic actions of oestrogen remain inconclusive. Cross-coupling of the oestrogen receptor to phosphoinositide 3-kinase signalling suggests a potentially critical non-nuclear action of the oestrogen receptor and considerably broadens our understanding of the cellular effects of oestrogen.