Minireview: Rapid Actions of Sex Steroids in the Endothelium

摘要

Theendotheliumisadynamicinterfacebetweenthebloodvesselandthecirculatingbloodthatplaysapivotalroleinvascularhomeostasis.Assuch,studiesonsexsteroidregulation of endothelial function are critical to understanding the role of sex steroids in cardiovascular health and disease. The classical model of steroid action involvesliganded steroid receptors binding to specific response elements on target genes to regulate gene transcription. In whole organisms, the time lag between steroidadministration and observable effects produced by newly synthesized protein is typically in the order of hours to days. And yet, some effects of steroids, such asvasodilatation, occur within seconds to minutes of steroid administration. Studies in multiple cell types have also shown that steroids can cause the rapid initiation ofmultiple signaling cascades and second messenger systems, prompting investigations into alternate, transcription independent mechanisms of steroid action. Studies ofthe endothelium over the past two decades have revealed fundamental mechanisms in rapid sex steroid signaling. In particular, endothelium-dependent vasodilatationby estradiol-induced activation of endothelial nitric oxide synthase has proven to be an uniquely informative model to study sex steroid signaling via classical sex steroidreceptorslocalizedtothecellmembrane.Despitethecomplexityoffeedbackandcrosstalkbetweenrapidsexsteroidsignalingandothermodesofsteroidaction,recentstudies in this field are facilitating the development of steroidal drugs that selectively target the ability of sex steroids to initiate signaling cascades.