Estrogens are essential hormones for the development and function of the reproductive tract, yet estrogen signaling plays crucial roles in non-reproductive tissues as well. In the cardiovascular system, estrogens regulate blood vessel tone and exert protective effects on the vasculature. We discovered that zebrafish embryos, an established model for cardiac conduction and development, respond to exogenous estradiol acutely with an increase in heart rate, a previously unappreciated role for estrogen signaling.
Estrogens act by binding to nuclear receptors (ERα, ERβ) that regulate gene expression directly or by binding to a G-protein coupled estrogen receptor (GPR30/GPER) that signals at the cell membrane. We found that estrogens regulate heart rate via GPER, independent of the canonical nuclear estrogen receptors.
We are working on identifying the specific signaling pathways by which GPER regulates heart rate, and determining whether GPER mutant zebrafish have additional cardiovascular defects associated with reduced heart rate.
Humans are exposed to structurally diverse estrogens through diet, pharmaceuticals and aquatic contamination. Using the zebrafish as a model, we are testing the effects of environmental estrogens on heart rate. Our results may identify a mechanism underlying the association between increased estrogen levels, higher resting heart rate and incidence of cardiac arrhythmia in humans.
Romano SN, Gorelick DA. Crosstalk between nuclear and G protein-coupled estrogen receptors. General & Comparative Endocrinology (2018)
Romano SN, Edwards HE, Souder JP, Ryan KJ, Cui X, Gorelick DA. G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish. PLOS Genetics (2017)