“Role of GPER in Estrogen‐Mediated Inhibition of Cardiomyocyte Hypertrophy.”

Estrogen is known to attenuate cardiac hypertrophy and heart failure in females. To understand how estrogen mediates its effects on the heart, it is important to understand how the cell receives the estrogen signal. Estrogen activates two classes of receptors: Nuclear Hormone Receptors (Estrogen Receptor Alpha (ER a ) and Estrogen Receptor Beta (ER β ) and a membrane bound G‐Protein Coupled Receptor for Estrogen (GPER or GPR30). It has not been established whether GPER plays a role in estrogen's ability to prevent cardiac hypertrophy or what that role may be. To determine if GPER plays a role in the antihypertrophic effects of estrogen, we have performed a series of in‐vitro experiments using primary rat cardiomyocyte cultures that have been serum starved for 24 hours and then exposed to the hypertrophic agent, Phenylephrine, in the presence or absence of a GPER specific inhibitor (G15) plus estrogen or the presence or absence of a GPER specific activator (G1) and compared to estrogen alone. The degree of hypertrophy was determined between the groups. Expression of known estrogen target genes were also assessed in cells exposed to the GPER specific activator by relative RT‐PCR. Taken together our results suggest that GPER does play a role in estrogen's antihypertrophic effects.