Genetic and pharmacologic strategies to determine the function of estrogen receptor alpha and estrogen receptor beta in cardiovascular system.
BACKGROUND
The biological functions of estrogens extend beyond the female and male reproductive tract, affecting the cardiovascular and renal systems. Traditional views on the role of postmenopausal hormone therapy (HT) in protecting against heart disease, which were challenged by clinical end point studies that found adverse effects of combined HT, are now being replaced by more differentiated concepts suggesting a beneficial role of early and unopposed HT that does not include a progestin.


OBJECTIVE
We reviewed recent insights, concepts, and research results on the biology of both estrogen receptor (ER) subtypes, ERalpha and ERbeta, in cardiac and vascular tissues. Knowledge of these ER subtypes is crucial to understanding gender and estrogen effects and to developing novel, exciting strategies that may have a profound clinical impact.


METHODS
This review focuses on in vivo studies and includes data presented at the August 2007 meeting of the American Physiological Society as well as data from a search of the MEDLINE and Ovid databases from January 1986 to November 2007. Search results were restricted to English-language publications, using the following search terms: estrogen, estrogen receptor alpha, estrogen receptor beta, estrogen receptor alpha agonist, estrogen receptor alpha antagonist, estrogen receptor beta agonist, estrogen receptor beta antagonist, PPT, DPN, heart, vasculature, ERKO mice, BERKO mice, transgenic mice, and knockout mice.


RESULTS
Genetic mouse models and pharmacologic studies that employed selective as well as nonselective ER agonists support the concept that both ER subtypes confer protective effects in experimental models of human heart disease, including hypertension, cardiac hypertrophy, and chronic heart failure.


CONCLUSIONS
Genetic models and novel ligands hold the promise of further improving our understanding of estrogen action in multiple tissues and organs. These efforts will ultimately enhance the safety and efficacy of HT and may also result in new applications for synthetic female sex hormone analogues.
Arias-Loza
Paula Anahi
PA
Department of Medicine, University of Würzburg, Würzburg, Germany.
Jazbutyte
Virginija
V
Pelzer
Theo
T
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D047628:Estrogen Receptor alpha / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000503:physiopathology; D011960:Receptors, Estrogen / Q000819:agonists
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen