Rapid estrogen signaling via GPER in human coronary artery smooth muscle

Abstract

Estrogen produces rapid, non‐genomic effects in coronary arteries, but the mechanisms underlying these responses are poorly understood. We had previously demonstrated that rapid vasodilatory effects of 17 beta‐estradiol on coronary arteries were mediated via the PI3 kinase – Akt signaling cascade (Han et al., Am. J. Physiol. 293:H314, 2007). We now identify a mechanism of acute estrogen signaling in human coronary artery smooth muscle cells (HCASMC) involving the G protein‐coupled estrogen receptor (GPER). HCASMC were grown in short‐term culture, and the effects of the GPER agonist, G1, were measured on activation of important downstream signaling molecules. Immunoblot studies demonstrated both basal and G1‐stimulated activation of mitogen‐activated protein kinase in HCASMC, and revealed that G1 acutely (2–5 minutes) stimulated phosphorylation of ERK1/2. Further, our studies also revealed that G1 stimulates Akt phosphorylation in HCASMC. We also found that G1, like 17beta‐estradiol, relaxed porcine arteries in vitro. These studies indicate a novel signaling mechanism for acute estrogen effects in human coronary arteries: stimulation of GPER, with subsequent activation of ERK1/2 and Akt. (supported by HL073890 and HL080402).