Reciprocality Between Estrogen Biology and Calcium Signaling in the Cardiovascular System.

17β-Estradiol (E) is the main estrogenic hormone in the body and exerts many cardiovascular protective effects. Via three receptors known to date, including estrogen receptors α (ERα) and β (ERβ) and the G protein-coupled estrogen receptor 1 (GPER, aka GPR30), E regulates numerous calcium-dependent activities in cardiovascular tissues. Nevertheless, effects of E and its receptors on components of the calcium signaling machinery (CSM), the underlying mechanisms, and the linked functional impact are only beginning to be elucidated. A picture is emerging of the reciprocality between estrogen biology and Ca signaling. Therein, E and GPER, via both E-dependent and E-independent actions, moderate Ca-dependent activities; in turn, ERα and GPER are regulated by Ca at the receptor level and downstream signaling via a feedforward loop. This article reviews current understanding of the effects of E and its receptors on the cardiovascular CSM and with a focus on mechanisms and combined functional impact. An overview of the main CSM components in cardiovascular tissues will be first provided, followed by a brief review of estrogen receptors and their Ca-dependent regulation. The effects of estrogenic agonists to stimulate acute Ca signals will then be reviewed. Subsequently, E-dependent and E-independent effects of GPER on components of the Ca signals triggered by other stimuli will be discussed. Finally, a case study will illustrate how the many mechanisms are coordinated to moderate Ca-dependent activities in the cardiovascular system.