Reciprocality Between Estrogen Biology and Calcium Signaling in the Cardiovascular System

17β-Estradiol (E₂) 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), E₂ regulates numerous calcium-dependent activities in cardiovascular tissues. Nevertheless, effects of E₂ 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 Ca²⁺ signaling. Therein, E₂ and GPER, via both E₂-dependent and E₂-independent actions, moderate Ca²⁺-dependent activities; in turn, ERα and GPER are regulated by Ca²⁺ at the receptor level and downstream signaling via a feedforward loop. This article reviews current understanding of the effects of E₂ and its receptors on the cardiovascular CSM and vice versa 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 Ca²⁺-dependent regulation. The effects of estrogenic agonists to stimulate acute Ca²⁺ signals will then be reviewed. Subsequently, E₂-dependent and E₂-independent effects of GPER on components of the Ca²⁺ signals triggered by other stimuli will be discussed. Finally, a case study will illustrate how the many mechanisms are coordinated to moderate Ca²⁺-dependent activities in the cardiovascular system.