Oestrogen and the cardiovascular system: the good, the bad and the puzzling

The concept that oestrogen replacement therapy is cardioprotective has been challenged recently by the negative results of randomized clinical trials in coronary heart disease. These data have come at a time of rapid advances in our understanding of the cellular mechanisms of oestrogen. in particula r,the cloning of the classical oestrogen receptor (ER alpha), the identific ation of a novel ER isoform (ER beta), the availability of specific ER alph a and ER beta knockout mice models, and the elucidation of receptor functio ns and signalling pathways linked to non-genomic actions of oestrogen are h elping to unravel this complex biology. In this article, these advances wil l be discussed with particular emphasis on the regulation of nitric oxide s ynthesis by oestrogen, Furthermore, the puzzling issues that have emerged a nd the potential for development of novel and specific therapeutic approach es will be highlighted.