Bushi Aisha, Ma Yixuan, Adu-Amankwaah Joseph, Wang Rong, Cui Fen, Xiao Rui, Zhao Jinming, Yuan Jinxiang, Tan Rubin
School international education, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
First Clinical Medical School, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Pharmacol Ther. 2025 May;269:108822. doi: 10.1016/j.pharmthera.2025.108822. Epub 2025 Feb 18.
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.
G蛋白偶联雌激素受体（GPER）目前因其在细胞信号传导中的关键作用而受到认可，它影响着多种生理过程和疾病状态。与经典雌激素受体不同，GPER表现出偏向性信号传导，即配体结合会触发某些选择性通路而非其他通路，这对细胞反应有重大影响。本综述探讨了由GPER介导的偏向性信号传导的细微机制，强调了其在心血管健康、神经功能、免疫调节和致癌过程中的相关性。尽管其具有关键意义，但与传统信号传导模式相比，通过GPER的偏向性信号传导仍未得到充分研究。我们探讨了在理解GPER信号传导特异性及其在各种疾病中的潜在治疗意义方面的最新进展。未来的研究方向旨在揭示偏向性信号传导的分子基础，开发选择性配体，并将这些见解转化为个性化治疗方法。利用GPER偏向性信号传导的治疗潜力是精准医学中一个有前景的前沿领域，为满足未满足的医疗需求提供了创新策略。
