Estrogen-independent activation of estrogen receptors.

Sex differences showing a lower prevalence and better outcome after ischemic stroke in women have been described, differences that are abrogated by natural or surgical menopause.1,2 High levels of endogenous estrogens in premenopausal women have been associated with reduced risk for a number of diseases, such as hypertension, diabetes mellitus, obesity, vascular disease, and stroke.2 The growing number of postmenopausal women attributed to shifts in world demographics also requires special action for the prevention and treatment of these conditions.2 Clinical and preclinical studies indicate that natural estrogens, such as 17 -estradiol, exert profound protective effects in the adult and the aging brain.1,3 Three proteins have been identified to mediate the effects of estrogens: estrogen receptor (ER) , ER , and G protein–coupled ER (GPER).2,4 Although expression and function of ER and ER have been well studied under physiological conditions, information about their function and expression under disease conditions, particularly in stroke,1 is still scarce.2,4