Illustrating rapid receptor-specific estrogen signaling.

Historically, estrogen receptor α and β have been connected to estrogen signaling on both genomic and non-genomic levels. Further evidence for estrogens’ involvement in rapid non-genomic signaling arose with the characterization consequent studies of a G protein-coupled estrogen receptor (GPER) which bound estrogen and subsequently induced downstream signaling. Through virtual screening and high-throughput analysis, several selective ligands have been discovered and shown possible physiological roles of GPER. Studies have revealed that this new mechanism of estrogen signaling may prove to be important in the treatment of estrogen sensitive cancers and vital in neuroprotection.

The long-term goal of this research is to design ligands that bind to GPER, identify selective agonists and antagonists, characterize their interactions with the receptor, analyze those interactions to develop biased ligands which can modulate receptor function, and determine their therapeutic potential. These studies are significant because further understanding of the receptor-ligand interaction could ultimately lead to new therapeutics and better understanding of several types of cancer and the neuroprotective effects of estrogens.