G protein-coupled estrogen receptor biased signaling in health and disease.

Abstract

G protein-coupled estrogen receptor (GPER) is now recognized for its pivotal role in cellular signaling, influencing diverse physiological processes and disease states. Unlike classical estrogen receptors, GPER exhibits biased signaling, wherein ligand binding triggers selective pathways over others, significantly impacting cellular responses. This review explores the nuanced mechanisms of biased signaling mediated by GPER, underscoring its relevance in cardiovascular health, neurological function, immune modulation, and oncogenic processes. Despite its critical implications, biased signaling through GPER remains underexplored compared to traditional signaling paradigms. We explore recent progress in understanding GPER signaling specificity and its potential therapeutic implications across various diseases. Future research directions aim to uncover the molecular basis of biased signaling, develop selective ligands, and translate these insights into personalized therapeutic approaches. Exploiting the therapeutic potential of GPER biased signaling represents a promising frontier in precision medicine, offering innovative strategies to address unmet medical needs.