Nongenomic actions of estrogens: Exciting opportunities for pharmacology

Estrogens, like other steroids, elicit a variety of rapid effects in many tissues in addition to their delayed action on gene expression in the cell nucleus. The rapid responses occur without participation of the genome, and are therefore termed nongenomic. Some of the estrogen induced effects acutely modulate vascular function and may contribute to the gender difference in cardiovascular susceptibility. While some actions may be mediated by novel, nonclassic receptors, the classic estrogen receptor has been shown to also act on signalling cascades. There are sparse examples for compounds structurally related to the endogenous hormone estradiol that bind to the estrogen receptor but may selectively elicit nongenomic responses. The further development of such selectively acting drugs holds much promise for better therapies with fewer side effects, e.g. for vascular malfunction, but also for estrogen-dependent cancer.