Cardioprotection by the female sex hormone -interaction with the β1-adrenoceptor and its signaling pathways

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Author:
Kathie A WONG()
Yan MA()
Wing-Tim CHENG()
Tak-Ming WONG(Tak-Ming WONG,Corresponding author.Tel:+86-852-28199194;Fax:+86-852-28559730;E-mail:wongtakm@hkucc.hku.hk)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 59, Issue 05, 2007
DOI:
Key Word:
estrogen; β1-adrenoceptor; Ca2+/calmodulin kinase Ⅱ; protein kinase A; cardioprotection; apoptosis

Abstract: 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 β-adrenoceptor stimulation. Estrogen replacement restores the response of OVX female rats to ischemic/β-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 β1-adrenoceptor. There is also evidence that estrogen suppresses the expression and activity of protein kinase A (PKA), a second messenger of the G8 protein/adenylyl cyclase/cAMP/PKA pathway which ultimately influences contractile function. There is also preliminary evidence that estrogen may suppress the activity of Ca2+/calmodulin kinase Ⅱδc isoform (CaMKII-δc), another downstream second messenger of the β1-adrenoceptor pathway, which is involved in PKA-independent cell apoptosis. Acute administration of estrogen at physiological level could inhibit myocardial β1-adrenoceptor and attenuate Ca2+ influx independent of the estrogen receptor. In addition, brain studies also show estrogen inhibits the activities activated by the β-adrenoceptor in brain regions responsible for the regulation of arterial blood pressure. Thus, it can be appreciated that the interaction between estrogen and the β1-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.

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