Nonnuclear actions of estrogen.
Estrogen has long been observed to endow cardiovascular protective effects, as evidenced by sex-specific differences in the incidence of hypertensive and coronary artery disease, the development of atherosclerosis, and myocardial remodeling after infarction. To exert its tissue-specific effects, the classic estrogen receptor (ER) functions as a ligand-dependent transcription factor. However, there is growing evidence that in response to 17beta-estradiol and heterologous signals, the ER can also mediate signaling cascades at the membrane and in the cytoplasm via various second messengers, such as receptor-mediated protein kinases. This review summarizes the current understanding of nonnuclear ER signaling and discusses the relevance to eliciting the beneficial cardiovascular effects of estrogen. These include vasodilation, inhibition of response to vessel injury, limiting myocardial injury after infarction, and attenuating cardiac hypertrophy. Defining the full repertoire of ER function promises to expose novel, highly specific targets for pharmacological interventions and may ultimately lead to the primary and secondary prevention of cardiovascular diseases.
Ho
Karen J
KJ
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass 02139, USA.
Liao
James K
JK
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D004967:Estrogens; D011960:Receptors, Estrogen