The G protein-coupled estrogen receptor (GPER), formerly known as G protein receptor 30 (GPR30), was identified as a novel estrogen receptor that mediates a rapid, non-genomic response to estrogens¹.

GPER is a G protein-coupled seven-transmembrane receptor. It is believed that the N-terminus is located outside of the cell, and that aspartic acid residues in the terminal region might be modified by glycosylation if GPER is localized in the plasma membrane. It is speculated that the ligand associates with the N-terminal domain to activate the receptor. Trimeric G protein is presumed to bind to the 3rd loop of the intracellular domain based on the molecular structure. A PDZ domain appears to be in the C-terminal region of GPER, but its physiological role is unknown².

GPER is widely distributed in the human body including: brain, liver, heart, lung, pancreas, placenta, blood vessels, bone, lymphoid tissue, as well as endometrial, ovarian and breast cancer. The receptor has been localized both in the plasma membrane and in the endoplasmic reticulum³.

It was found that GPER is rapidly induced in the cardiomyocyte ischemia model, and that its induction is associated with apoptotic cell death during ischemia and reperfusion⁴. In addition, the GPER mediates estrogenic signaling in breast cancer cells and cancer-associated fibroblasts (CAF) that contribute to cancer progression⁵.