Dear Editor,

Estrogen is a pivotal hormone in human physiology, orchestrating a wide range of biological processes ranging from reproductive functions to cardiovascular health and bone integrity.¹ The orphan receptor GPR30 has been hypothetically conceived as a G protein-coupled estrogen receptor that directly binds estrogen,^2,3,4 offering mechanisms explaining non-genomic effects and tissue-selectivity of estrogen signaling.⁵ This provocative idea has a profound impact on our understanding of rapid estrogen biology.^6,7 However, recent studies have produced conflicting results about whether GPR30 truly serves as an independent estrogen receptor.^{8,9,10,11,12,13} In this work, we combined biochemical, structural, and functional approaches to directly test whether GPR30 interacts with and signals in response to estrogen and estrogen-related compounds.

亲爱的编辑，

雌激素是人体生理学中的关键激素，协调从生殖功能到心血管健康和骨骼完整性的广泛生物过程。¹孤儿受体 GPR30 被假设为一种 G 蛋白偶联雌激素受体，可直接结合雌激素，^2,3,4提供解释雌激素信号传导的非基因组效应和组织选择性的机制。⁵这一具有争议性的想法对我们对快速雌激素生物学的理解产生了深远的影响。^6,7然而，最近的研究对于 GPR30 是否真正充当独立的雌激素受体产生了相互矛盾的结果。^{8,9,10,11,12,13}在这项工作中，我们结合了生化、结构和功能方法来直接测试 GPR30 是否与雌激素和雌激素相关化合物相互作用并发出信号。