Cardioprotection by the female sex hormone -- interaction with the beta₁-adrenoceptor and its signaling pathways.
Estrogen is a steroid and the predominant female sex hormone in the body. Ovariectomised (OVX) adult female rats exhibit greater myocardial injury compared to the sham rats following ischemic insult in the presence of beta-adrenoceptor stimulation. Estrogen replacement restores the response of OVX female rats to ischemic/beta-adrenoceptor stimulation to that of normal female rats, providing evidence for a cardioprotective role of estrogen during ischemic insult. The protective effect is due to down-regulation of the beta(1)-adrenoceptor. There is also evidence that estrogen suppresses the expression and activity of protein kinase A (PKA), a second messenger of the G(s) protein/adenylyl cyclase/cAMP/PKA pathway which ultimately influences contractile function. There is also preliminary evidence that estrogen may suppress the activity of Ca(2+)/calmodulin kinase II deltac isoform (CaMKII-deltac), another downstream second messenger of the beta(1)-adrenoceptor pathway, which is involved in PKA-independent cell apoptosis. Acute administration of estrogen at physiological level could inhibit myocardial beta(1)-adrenoceptor and attenuate Ca(2+) influx independent of the estrogen receptor. In addition, brain studies also show estrogen inhibits the activities activated by the beta-adrenoceptor in brain regions responsible for the regulation of arterial blood pressure. Thus, it can be appreciated that the interaction between estrogen and the beta(1)-adrenoceptor and its signaling pathways is a complex one. Estrogen plays an important role not only in reproduction but also in other regulatory functions such as cardioprotection.
Wong
Kathie A
KA
Department of Physiology, the University of Hong Kong, Hong Kong, China.
Ma
Yan
Y
Cheng
Wing-Tim
WT
Wong
Tak-Ming
TM
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases; D015536:Down-Regulation; D004967:Estrogens / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000517:prevention & control; D009206:Myocardium; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D015398:Signal Transduction
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D018342:Receptors, Adrenergic, beta-1; D017868:Cyclic AMP-Dependent Protein Kinases