Membrane estrogen receptor (mER) (mER)

Membrane estrogen receptors (mERs) are a class of cell surface receptors that mediate the rapid, non-genomic effects of estrogen, distinct from the slower transcriptional actions of nuclear estrogen receptors [1, 12]. The most well-characterized member is the G protein-coupled estrogen receptor 1 (GPER1, formerly GPR30), though membrane-localized versions of the classical receptors ER-alpha and ER-beta also contribute to this signaling pool [1, 13]. Upon activation by 17β-estradiol or other ligands, mERs trigger intracellular cascades such as cAMP production, calcium mobilization, and the transactivation of the epidermal growth factor receptor (EGFR), which subsequently activates the MAPK/ERK and PI3K/Akt pathways [6, 10]. These receptors play critical roles in diverse physiological processes, including vasodilation, cardioprotection, neuroprotection, and metabolic homeostasis [10, 15]. In disease, mERs are heavily implicated in the progression and endocrine resistance of various cancers, particularly breast and endometrial malignancies [7, 11]. Interestingly, common anti-estrogen therapies like tamoxifen and fulvestrant act as agonists for GPER1, which may contribute to therapeutic resistance in some patients [8, 17].

Other names

G protein-coupled estrogen receptor 1GPER1GPR30mER-alphamER-betaER-XGq-mER

Agonism or antagonism of G protein-coupled receptor signaling, leading to rapid activation of intracellular cascades including cAMP production, calcium mobilization, and Src-mediated transactivation of the epidermal growth factor receptor (EGFR), which subsequently triggers MAPK/ERK and PI3K/Akt pathways [6, 10, 15].