Affinage

GPER1

G-protein coupled estrogen receptor 1 · UniProt Q99527

Length
375 aa
Mass
42.2 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPER1 (GPR30) is a seven-transmembrane G protein-coupled receptor that functions as a membrane estrogen receptor, mediating rapid non-genomic responses to 17β-estradiol and synthetic ligands across diverse tissues including breast, brain, vasculature, and reproductive organs. It couples to multiple G protein families—Gs to stimulate adenylyl cyclase/cAMP, Gi/o to activate ERK1/2 via both constitutive PDZ/AKAP5-dependent and ligand-stimulated mechanisms, and Gq to engage phospholipase C/PKC—and transactivates EGFR through Gβγ-dependent release of membrane-tethered HB-EGF, converging on PI3K/Akt, MAPK, PKA/CREB, and NF-κB signaling cascades (PMID:22495674, PMID:28450397, PMID:36400433). These signaling outputs mediate cell-type-specific functions including BDNF-dependent synaptic plasticity and AMPA receptor internalization in hippocampus, fibronectin matrix assembly via integrin α5β1-Shc complexes, PFKFB3-dependent angiogenesis, SPOP/Cullin3-mediated ERα proteasomal degradation, steroidogenesis regulation, and calcium channel modulation in vascular smooth muscle (PMID:26391661, PMID:25096985, PMID:28348059, PMID:33069770, PMID:24080531). GPER1 activation during pregnancy suppresses type I interferon signaling in reproductive and fetal tissues, and genetic loss of GPER1 in mice causes fetal demise during maternal inflammation (PMID:33446553).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2012 High

    Establishing that GPER1 is a bona fide Gs-coupled receptor for estrogen resolved the question of whether non-genomic estrogen signaling operates through a dedicated GPCR rather than through nuclear ERs alone, defining its core mechanism as adenylyl cyclase stimulation and Gβγ-dependent HB-EGF release for EGFR transactivation.

    Evidence Convergent pharmacological, knockdown, and adenylyl cyclase assay studies synthesized from multiple labs

    PMID:22495674

    Open questions at the time
    • Structural basis of estrogen binding to a GPCR fold not resolved
    • Relative contribution of Gs vs. other G proteins in native tissues unclear
  2. 2013 Medium

    Defining GPER1's vascular signaling repertoire revealed that the same receptor drives opposing vascular responses—vasorelaxation via Src/EGFR/Akt in aorta and vasoconstriction via ROCK/PKC/MAPK/VOCCs in kidney—establishing GPER1 as a context-dependent modulator of vascular tone and calcium handling.

    Evidence Pharmacological dissection with extensive inhibitor panels in isolated rat aortic rings, perfused kidney, and vascular smooth muscle Ca²⁺ imaging

    PMID:23376418 PMID:24028616 PMID:24080531

    Open questions at the time
    • Molecular determinants of tissue-specific G protein coupling not identified
    • No genetic validation of receptor dependence in vascular models
    • Endogenous ligand concentrations in vascular beds not measured
  3. 2013 High

    Demonstration that GPER1 stimulation promotes fibronectin matrix assembly through HB-EGF/integrin α5β1/Shc signaling—with Shc Y317F phosphorylation mutant abolishing anchorage-independent growth—established GPER1 as a direct link between estrogen signaling and extracellular matrix remodeling in breast cancer.

    Evidence Co-immunoprecipitation, Shc Y317F mutant, haptotaxis, and anchorage-independent growth assays in breast cancer cells

    PMID:25096985

    Open questions at the time
    • Whether integrin α5β1-Shc axis operates in non-cancer epithelial cells unknown
    • Direct Shc binding site on GPER1 signaling complex not mapped
  4. 2014 Medium

    Identification of GPER1's role in modulating serotonin receptor desensitization through posttranslational modification of RGSz1 and sequestration of Gαz in detergent-resistant membrane microdomains provided a molecular mechanism for estrogen-serotonin crosstalk relevant to neuroendocrine regulation.

    Evidence Subcellular fractionation, RGSz1 SUMOylation/glycosylation analysis, and in vivo oxytocin/ACTH response after G-1 administration

    PMID:25402859

    Open questions at the time
    • Direct physical interaction between GPER1 and RGSz1 not demonstrated
    • Enzymatic machinery mediating RGSz1 SUMOylation downstream of GPER1 not identified
  5. 2014 Medium

    Showing that GPER1 mediates estradiol's effects on steroid hormone production—inhibiting aldosterone synthesis via PKA signaling and reducing testosterone in Leydig cells—expanded the receptor's role beyond classical signal transduction to endocrine homeostasis.

    Evidence GPER1 siRNA, selective agonist G-1, PKA inhibitor in HAC15 adrenocortical cells; G-1 treatment of isolated rat Leydig cells and human testicular tissue

    PMID:24736568 PMID:25167221

    Open questions at the time
    • Steroidogenic enzyme targets directly regulated by GPER1-PKA axis not fully mapped
    • Physiological relevance under normal endogenous estrogen levels not established
  6. 2015 High

    Discovery that GPER1 activation in hippocampus triggers BDNF release, transient Arc translation, GluA1 AMPA receptor internalization and subsequent proteasomal degradation established a complete molecular cascade through which estrogen rapidly modulates synaptic plasticity.

    Evidence Pharmacological dissection combined with electrophysiological LTD recording and biochemical measurement of Arc, GluA1, and BDNF in hippocampal slices

    PMID:25980457 PMID:26391661

    Open questions at the time
    • Whether GPER1 acts cell-autonomously in neurons vs. through glia not resolved
    • Structural mechanism of GPER1-BDNF release coupling unknown
  7. 2017 High

    Dissection of two distinct ERK1/2 activation modes—a constitutive PDZ/AKAP5/Gi/o-dependent pathway requiring PI3K and a ligand-stimulated PDZ-independent pathway—resolved how GPER1 maintains basal signaling tone while retaining stimulus-responsiveness, and identified SAP97 and AKAP5 as scaffold partners anchoring GPER1 at the plasma membrane.

    Evidence PDZ motif deletion mutants, AKAP5/SAP97 knockdown, pertussis toxin, pathway inhibitors in receptor-expressing cells

    PMID:28450397

    Open questions at the time
    • Crystal or cryo-EM structure of GPER1-AKAP5 complex not available
    • Whether PDZ-dependent constitutive signaling occurs in all GPER1-expressing cell types unknown
  8. 2017 Medium

    Identification of PFKFB3 as the downstream effector through which GPER1 drives endothelial angiogenesis linked GPER1 signaling to glycolytic metabolic reprogramming in vascular biology.

    Evidence GPER1 siRNA and G-15 antagonist abolish PFKFB3 upregulation; PFKFB3 inhibitor blocks GPER1-mediated HUVEC migration and tube formation

    PMID:28348059

    Open questions at the time
    • Transcription factor(s) mediating GPER1-dependent PFKFB3 upregulation not identified
    • In vivo angiogenesis validation in GPER1 knockout mice not performed
  9. 2019 High

    Demonstrating that GPER1 activates PRKACA to phosphorylate MORC2-T582, protecting it from chaperone-mediated autophagy and promoting antiestrogen resistance, revealed a direct mechanism linking GPER1 to chromatin regulator stability and therapy resistance in breast cancer.

    Evidence Co-immunoprecipitation, T582A phospho-mutant, siRNA knockdown, rescue with WT vs. mutant MORC2

    PMID:32401166

    Open questions at the time
    • Whether MORC2 stabilization is a general GPER1 output or breast cancer-specific unknown
    • Upstream mechanism selecting MORC2 as PRKACA substrate in GPER1 context not defined
  10. 2020 High

    Establishing that GPER1 promotes ERα degradation through upregulation of the SPOP/Cullin3 E3 ubiquitin ligase adaptor provided a molecular mechanism for the functional antagonism between GPER1 and classical nuclear estrogen receptor signaling.

    Evidence SPOP siRNA abrogates GPER1-induced ERα ubiquitination and degradation; GPER1 agonist G-1 suppresses ERα-mediated transcription without affecting ERα mRNA

    PMID:33069770

    Open questions at the time
    • Whether GPER1 directly regulates SPOP transcription or protein stability not distinguished
    • In vivo tissue-specific impact on ERα levels in GPER1 knockout not assessed
  11. 2021 High

    Genetic knockout studies established that GPER1 suppresses type I interferon signaling in reproductive and fetal tissues during pregnancy, and that loss of GPER1 leads to fetal demise during maternal inflammation—demonstrating an essential physiological role beyond cancer biology.

    Evidence GPER1 knockout mice, maternal inflammation model, IFN signaling assays, fetal development assessment

    PMID:33446553

    Open questions at the time
    • Molecular mechanism by which GPER1 suppresses IFN signaling not defined
    • Cell types responsible for IFN suppression in reproductive tract not identified
  12. 2022 High

    Demonstrating canonical Gq-PLC coupling and rapid agonist-induced internalization in an unbiased multiplex screen, with cell-line-dependent plasma membrane integration, clarified that GPER1's G protein selectivity and subcellular localization are not fixed properties but vary by cellular context.

    Evidence Multiplex GPCR Ca²⁺ screen, Gq inhibitor YM-254890, PKC/ERK assays, fluorescent fusion protein localization across multiple cell lines

    PMID:36400433

    Open questions at the time
    • Determinants of cell-type-specific G protein coupling preference not identified
    • Structural basis for Gq vs. Gs vs. Gi/o selectivity unknown
  13. 2023 Medium

    Expansion of GPER1's immunomodulatory role to macrophage polarization and renal fibrosis—where GPER1 activation suppresses M1/M2 polarization via MAPK inactivation and GPER1 deletion accelerates fibrosis—extended the receptor's physiological relevance to tissue repair and inflammation beyond pregnancy.

    Evidence GPER1 agonist and knockout mice in UUO renal fibrosis model, RNA-seq, macrophage polarization and co-culture assays

    PMID:38086848

    Open questions at the time
    • Direct GPER1 signaling targets in macrophages upstream of MAPK inactivation not mapped
    • Whether anti-fibrotic effect is macrophage-autonomous or involves other cell types not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for GPER1's estrogen binding within a GPCR fold, the molecular determinants governing cell-type-specific G protein coupling selectivity, and the relative physiological contributions of constitutive versus ligand-stimulated signaling in vivo remain unresolved.
  • No high-resolution structure of GPER1 with or without ligand
  • In vivo contribution of constitutive PDZ/AKAP5-mediated signaling to physiology unknown
  • Mechanism of biased agonism at GPER1 (e.g., aldosterone vs. estradiol) not structurally or biochemically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-168256 Immune System 4 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2
Partners
AKAP5AMFESR1MORC2RELASAP97SPOP

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 GPER1/GPR30 is a Gs-coupled heptahelical transmembrane receptor that promotes specific binding of estrogens, stimulates adenylyl cyclase, and mediates Gβγ-subunit protein-dependent release of membrane-tethered heparan-bound EGF (HB-EGF), constituting its core non-genomic signaling mechanism. cDNA cloning, pharmacological agonist/antagonist studies, receptor knockdown, adenylyl cyclase assay Endocrinology High 22495674
2017 GPER1 increases ERK1/2 activity via two Gi/o-mediated mechanisms: a PDZ motif-dependent constitutive mechanism requiring AKAP5 interaction, and a PDZ-independent G-1-stimulated mechanism; the constitutive mechanism requires PI3K but not EGFR transactivation, and involves a protein phosphatase. PDZ motif deletion mutants, AKAP5 knockdown, pertussis toxin, wortmannin, AG1478, FK506, okadaic acid, pharmacological inhibitors in receptor-expressing cells The Journal of biological chemistry High 28450397
2022 In overexpressing HEK293 cells, GPR30/GPER1 couples canonically to Gq-phospholipase C, activating PKC and ERK, and undergoes rapid receptor internalization upon agonist exposure; plasma membrane integration and functional responses are cell-line-dependent. Multiplex GPCR Ca2+ screen, Gq inhibitor YM-254890, PKC and ERK assays, fluorescent fusion protein localization in multiple cell lines Molecular pharmacology High 36400433
2017 GPER1 constitutively interacts via its C-terminal type I PDZ motif with SAP97 and AKAP5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive, Gi/o-independent decrease in cAMP production. Co-immunoprecipitation, PDZ motif deletion, siRNA knockdown of SAP97 and AKAP5, cAMP assay, pertussis toxin The Journal of biological chemistry High 28450397
2019 GPER1 activates PRKACA (protein kinase A catalytic subunit alpha), which phosphorylates MORC2 at threonine 582; phosphorylated MORC2 has reduced interaction with the CMA components HSPA8 and LAMP2A, protecting it from lysosomal degradation and thereby promoting breast cancer cell proliferation and antiestrogen resistance. Co-immunoprecipitation, phosphorylation mutant (T582A), siRNA knockdown, rescue experiments with WT vs. mutant MORC2 Autophagy High 32401166
2013 GPER1 stimulation by estradiol promotes fibronectin (FN) matrix assembly via release of HB-EGF, recruits integrin α5β1 to fibrillar adhesions, forms integrin α5β1-Shc adaptor protein complexes, enhances focal adhesion and actin stress fiber formation, and enables FN-dependent anchorage-independent growth; mutation of Shc Y317F abolishes these effects. Co-immunoprecipitation, Shc Y317F phosphorylation mutant, haptotaxis assay, hanging drop anchorage-independent growth assay, pharmacological agonist/antagonist Hormones & cancer High 25096985
2015 GPER1 activation by estradiol or G-1 rapidly induces BDNF release in hippocampal CA3 field, leading to transient Arc protein translation and GluA1-containing AMPA receptor internalization; subsequent mGluR1 activation triggers LTD involving ubiquitination and proteasome-mediated GluA1 degradation. Selective agonist/antagonist pharmacology, BDNF measurement, Arc and GluA1 immunoblotting, proteasome inhibition, LTD electrophysiology The Journal of cell biology High 26391661
2015 GPER1 activation by estradiol or G-1 stimulates adenylyl cyclase/cAMP production, which activates ERK/MAPK signaling and upregulates Runx2 expression in osteoblasts to promote bone regeneration. cAMP measurement, selective GPER1 antagonist G15 blockade, MAPK inhibitors, Runx2 protein/gene expression, in vivo bone drill-hole model The Journal of nutritional biochemistry Medium 26345541
2013 GPER1 agonist G-1 induces vasorelaxation in rat aorta through endothelium-dependent, Src-mediated EGFR transactivation and downstream Akt signaling, independent of ERα/ERβ and PI3K or ERK pathways. Isolated rat aortic ring organ bath pharmacology with selective inhibitors (L-NAME, AG1478, DAPH, Src inhibitor, Akt inhibitor VIII, LY294002, PD98059, G15, MPP, ICI182780) The Journal of pharmacy and pharmacology Medium 24028616
2013 GPER1 mediates vasoconstriction in isolated perfused rat kidney via signaling pathways involving ROCK, PKC, p38 MAPK, p42/44 MAPK, tyrosine kinase, EGFR kinase, and voltage-operated Ca2+ channels (VOCCs), but not JNK or PI3K. Isolated perfused rat kidney pharmacology with selective inhibitors (Y-27632, genistein, SB203580, PD98059, GF109203X, SP600125, LY294002, nifedipine, AG-1478, G15), endothelium removal, Western blot for GPER1 expression European journal of pharmacology Medium 23376418
2013 GPER1 agonist G-1 regulates vascular smooth muscle cell Ca2+ handling by reducing spontaneous Ca2+ spike activity and blocking L-type voltage-sensitive Ca2+ channel-mediated Ca2+ influx, in a GPER1-dependent manner. Live Ca2+ imaging in A7r5 vascular smooth muscle cells, nifedipine comparison, G15 antagonist blockade, KCl-evoked Ca2+ measurement Journal of vascular research Medium 24080531
2014 GPER1 mediates estradiol-induced inhibition of aldosterone synthesis through protein kinase A (PKA) signaling; silencing GPER1 lowers aldosterone synthase expression, while G-1 mimics the stimulatory effect of estradiol when ERβ is blocked, and a PKA inhibitor abrogates the G-1 effect. GPER1 siRNA knockdown, ERβ siRNA knockdown, selective agonist G-1, antagonist G-15, PKA inhibitor, aldosterone synthase expression and aldosterone production measurement in HAC15 adrenocortical cells Endocrinology Medium 25167221
2014 GPER-1 activation lowers testosterone production by 20-30% in isolated rat Leydig cells and human testicular tissue, via a direct effect on steroidogenesis independent of cell viability. Isolated rat Leydig cells, human testicular tissue, GPER-1 selective agonist G-1, radioimmunoassay for testosterone, ICI 182,780, MTS cell viability assay PloS one Medium 24736568
2015 GPER1 agonist G-1 attenuates endothelial cell proliferation by inhibiting DNA synthesis and accumulating cells in S and G2/M phases; this effect is GPER1-dependent as confirmed by siRNA knockdown and is independent of ERK/MAPK activity. GPER1 siRNA knockdown, flow cytometry cell-cycle analysis, BrdU DNA synthesis assay, ERK inhibitor PD98059, multiple endothelial cell lines Journal of vascular research Medium 21273787
2015 GPER1 stimulation with GPER1 agonist G1 increased ERK activity in hippocampal slices; the GPER1 antagonist G15 blocked estradiol-mediated enhancement of synaptic transmission; G1 prior application occluded further estradiol-induced synaptic enhancement, and ERK inhibition blocked the response. Extracellular field potential recording in hippocampal slices from WT, ERαKO, and ERβKO mice; selective agonists G1, PPT, DPN; G15 antagonist; ERK inhibitor Hippocampus Medium 25980457
2019 Autocrine motility factor (AMF) physically binds to GPER1 and the formed complex translocates from the plasma membrane to the cytoplasm, activating PI3K/AKT signaling to promote endometrial cancer cell growth. Co-immunoprecipitation, immunofluorescence co-localization, yeast two-hybrid assay, iTRAQ proteomics, xenograft mouse model Cell communication and signaling : CCS Medium 30836961
2021 GPER1 activation during pregnancy suppresses type I interferon (IFN) signaling disproportionately in reproductive and fetal tissues; GPER1 inactivation in mice halted fetal development and promoted fetal demise specifically in the context of maternal inflammation. Genetic GPER1 knockout mice, maternal inflammation model, IFN signaling assays, fetal development assessment Science (New York, N.Y.) High 33446553
2020 GPER1 mediates ubiquitin-proteasome-dependent degradation of ERα by upregulating the Cullin3-based E3 ubiquitin ligase adaptor SPOP; SPOP depletion abrogates GPER1-induced ERα ubiquitination and degradation, and GPER1 activation suppresses ERα-mediated transcription without affecting ERα mRNA. Co-immunoprecipitation, ubiquitination assay, SPOP siRNA knockdown, ERα protein/mRNA measurement, selective GPER1 agonist G-1, in vitro and in vivo breast cancer models Cancer letters High 33069770
2014 GPER1 stimulation alters posttranslational modification of RGSz1, increasing the high-molecular-weight (SUMOylated and glycosylated) RGSz1 isoform localized in detergent-resistant membrane microdomains (DRM), thereby functionally uncoupling 5-HT1AR signaling by sequestering active Gαz. G-1 selective agonist, subcellular fractionation (DRM isolation), Western blot for RGSz1 isoforms, SUMOylation/glycosylation analysis, in vivo oxytocin and ACTH hormone response assays Neuroendocrinology Medium 25402859
2017 GPER1 mediates estradiol-induced angiogenesis in HUVECs by upregulating the glycolytic enzyme PFKFB3; GPER1 antagonist G-15 or GPER1 siRNA abolishes the PFKFB3 upregulation, and PFKFB3 inhibition blocks GPER1-mediated HUVEC migration. GPER1 siRNA knockdown, G-15 antagonist, PFKFB3 inhibitor (3PO), selective G-1 agonist, angiogenesis assays (migration, tube formation), PFKFB3 protein expression The Journal of pharmacology and experimental therapeutics Medium 28348059
2015 GPER1 activation by estradiol or G-1 in ER-negative breast cancer cells (SKBR3, BT-20) activates ERK, AKT, and NF-κB, leading to increased IL-8 secretion; blockade or knockdown of GPER1 inhibits these pathways and attenuates cancer cell migration and invasion, with downstream CXCR1 involvement. GPER1 siRNA knockdown, specific pathway inhibitors, IL-8 ELISA, migration/invasion assays, NF-κB translocation assay The Journal of steroid biochemistry and molecular biology Medium 23907016
2015 GPER1 mediates E2-induced inhibition of ERK1/2 (constitutively activated in granulosa cell tumors) through non-genomic mechanisms, suppressing migration and invasion of metastatic GCT cells; RNA silencing and pharmacological inhibition of GPER1 abrogated this effect. GPER1 siRNA, pharmacological agonist/antagonist, ERK1/2 phosphorylation assay, migration and invasion assays in KGN and COV434 cells Carcinogenesis Medium 25823895
2016 GPER1 activation reduces BBB permeability after global cerebral ischemia by preserving tight junction proteins (occludin and claudin-5) and decreasing VEGF-A expression in hippocampal CA1. Intracerebroventricular G1 agonist injection in ovariectomized rats, IgG extravasation assay, Western blot for occludin, claudin-5, VEGF-A Biochemical and biophysical research communications Medium 27311857
2016 GPER1 mediates estrogen-induced neuroprotection against oxygen-glucose deprivation (OGD) in primary hippocampal neurons via PI3K/Akt-dependent Ask1 inhibition; GPER1 knockdown diminishes and GPER1 overexpression potentiates neuroprotection by membrane-impermeable E2-BSA. GPER1 siRNA knockdown, GPER1 overexpression, E2-BSA (membrane-impermeable estradiol), PI3K/Akt inhibitor LY294002, cell viability assay in primary neurons Neuroscience Medium 27113328
2014 Insulin transactivates the GPER1 promoter and increases GPER1 mRNA and protein expression through a PRKCD/MAPK1/c-Fos/AP1 signaling pathway in leiomyosarcoma cells and cancer-associated fibroblasts; GPER1 upregulation by insulin in turn mediates cell migration through CTGF and potentiates estrogen-stimulated glucose uptake and cell cycle progression. GPER1 promoter-luciferase reporter assay, pharmacological inhibitors, gene-silencing experiments, migration assays, glucose uptake assay Endocrine-related cancer Medium 25012984
2015 GPER1 inhibition in breast cancer cells via siRNA knockdown suppresses GPER1-mediated IGFBP-1 induction; 4-OHT activates GPER1, which signals through CREB to induce extracellular IGFBP-1 accumulation, which in turn inhibits IGF-1/Akt signaling. GPER1 siRNA knockdown, conditioned medium transfer assay, IGFBP-1 neutralization, CREB pathway analysis, phospho-Akt measurement Molecular and cellular endocrinology Medium 26690777
2014 GPER1 and ERα36 (36 kDa splice variant) physically interact, and in human monocytes, ligand-activated ERα36 directly interacts with NF-κB p65 subunit in the nucleus to inhibit LPS-induced IL-6; GPER1 acts as a co-regulator in this process as its inhibition blocks the estrogen effect on IL-6. Co-immunoprecipitation, GPER1 selective inhibitor, siRNA knockdown, NF-κB reporter assay, IL-6 ELISA in human primary monocytes Journal of leukocyte biology Medium 26394816
2021 In breast cancer cells, ERα36 and GPER1 physically interact (especially after LPS treatment), and GPER1 directly interacts with NF-κB; together ERα36 and GPER1 inhibit TLR4/NF-κB-mediated inflammation independently of ERα66. Co-immunoprecipitation, ERα36 overexpression, siRNA knockdown of ERα36 and GPER1, NF-κB reporter assay, cytokine (TNFα, IL-6) measurement International journal of molecular sciences Medium 34299224
2018 GPER1 deletion in salt-sensitive hypertensive rats by CRISPR/Cas9 reduced blood pressure and was associated with altered gut microbiota and short-chain fatty acids; microbiotal transplantation from Gper1+/+ hypertensive rats reversed the cardiovascular protection of Gper1 deletion, demonstrating that GPER1 promotes microbiota alterations contributing to cardiovascular pathology. Multiplexed guide RNA CRISPR/Cas9 genomic excision of Gper1, fecal microbiota transplantation, blood pressure measurement, vascular relaxation assay, short-chain fatty acid measurement Hypertension (Dallas, Tex. : 1979) Medium 30354811
2014 GPER1 and CerS4/CerS5 promoter activation by 17β-estradiol is mediated through AP-1 (c-Jun/c-Fos dimerization); promoter deletion and mutation constructs demonstrated this AP-1 dependence, and GPER1 co-transfection modulated ceramide synthase promoter activities. Luciferase reporter assay with promoter deletion and mutation constructs, GPER1 co-transfection, fulvestrant inhibition, MCF-7 and MDA-MB-231 cells Biochemical pharmacology Medium 25451689
2019 GPER1 overexpression in MCF-7 breast cancer cells causes G1 cell cycle arrest, induces autophagy/mitophagy, reduces basal respiration and glycolysis; stable GPER1 overexpression reduces CerS4, CerS5, and CerS6 promoter activity with the CerS5 effect mediated by GSK-3β signaling. Stable GPER1 overexpression, cell cycle analysis, autophagy assays, Seahorse metabolic assay, luciferase promoter assay, GSK-3β signaling inhibition The international journal of biochemistry & cell biology Medium 31082617
2022 In mucopolysaccharidosis (MPS) I cells, GPER1 forms anomalous aggregates that co-localize with glycosaminoglycans (GAGs); enzyme replacement therapy that degrades GAGs causes disappearance of the GPER1 aggregates, indicating that GAG accumulation drives GPER1 aggregation rather than altered protein expression. Transcriptomic analysis, immunofluorescence localization, enzyme replacement treatment, correlation with GAG levels in MPS I and MPS II patient-derived cells European journal of cell biology Medium 35537249
2016 In embryonic hippocampal mHippoE-18 cells, endogenous GPER1 mediates 17β-estradiol-induced potentiation of forskolin-stimulated cAMP; however, GPER1-selective antagonists G15 and G36 paradoxically switch this to an inhibitory response, and aldosterone mimics the inhibitory coupling even without antagonists, demonstrating biased agonism/antagonism dependent on ligand identity. cAMP assay with selective GPER1 agonists (G1, tamoxifen, ICI182780) and antagonists (G15, G36), ERα/ERβ agonists (PPT, DPN) in an endogenously expressing hippocampal cell line PloS one Medium 26998610
2020 GPER1 knockdown in gastric cancer cells suppresses proliferation, migration, and invasion by inhibiting PI3K/AKT-mediated EMT; PI3K activator 740Y-P reverses the effects of GPER1 knockdown on EMT markers, placing GPER1 upstream of PI3K/AKT in this pathway. GPER1 siRNA knockdown, GPER1 overexpression, PI3K activator rescue, EMT marker Western blot, proliferation/migration/invasion assays Frontiers in cell and developmental biology Medium 33425895
2022 BPS (bisphenol S) induces Agrp mRNA expression in hypothalamic neurons through GPER1 signaling; GPER1 antagonist G15 prevents BPS-mediated Agrp upregulation independently of Atf3 and Klf4 induction. G15 pharmacological antagonism, BPS treatment of immortalized hypothalamic cell lines, RT-PCR for Agrp and multiple transcription factors Molecular and cellular endocrinology Medium 35569583
2023 GPER1 activation by G-1 in macrophages reduces M1 and M2 macrophage polarization, downregulates immune pathway activation and inactivates MAPK pathways, thereby reducing tubular epithelial cell injury and fibroblast ECM production in co-culture; GPER1 deletion in male UUO mice accelerates renal fibrosis. GPER1 agonist G-1 in OVX and male UUO mouse models, Gper1 knockout mice, RNA-sequencing, immunoblotting for MAPK pathway, macrophage polarization assays, co-culture experiments Cell death & disease Medium 38086848
2023 GPER1 activation by G-1 in multiple myeloma cells triggers apoptosis and upregulates the miR-29b oncosuppressive network by blunting a miR-29b-Sp1 feedback loop; this reduces MM growth in xenograft models even in bortezomib-resistant cells. Selective GPER1 agonist G-1, miR-29b expression analysis, Sp1 pathway assessment, apoptosis assay, xenograft mouse models Cells Medium 37759449
2023 E2 enhances melatonin synthesis (AANAT expression) in human trophoblast cells through GPER1-PKA-CREB signaling pathway; pharmacological dissection established this specific receptor-signaling axis in placental hormone homeostasis. Primary human trophoblast cell culture, GPER1 agonist/antagonist pharmacology, PKA inhibitor, CREB pathway analysis, AANAT expression measurement Journal of pineal research Medium 37746893
2013 GPER1 mediates ROCK-2 upregulation in rat coronary vascular endothelial cells via EGFR transactivation and Gi/o protein signaling, as evidenced by inhibition with pertussis toxin (PTX), AG-1478, G-15 antagonist, and actinomycin-D; ERα and ERβ selective agonists had no effect on ROCK-2. Western blot for ROCK-2 and GPER1, pertussis toxin, AG-1478, G-15 antagonist, actinomycin-D, primary rat coronary vascular endothelial cells Endocrine regulations Low 23641788
2019 GPER1 activation by G-1 protects retinal ganglion cells from NMDA-induced apoptosis via PI3K/Akt pathway; pharmacological PI3K/Akt inhibitor LY294002 counteracts G-1 protection, and antibody array shows decreased Bad, Caspase 3, Caspase 7, Smad2, P53, and TAK1 in G-1-treated retinae. NMDA and AOH mouse models, G-1 agonist, G-15 antagonist, tamoxifen (ERα/ERβ blocker), LY294002 (PI3K inhibitor), immunofluorescence, TUNEL, antibody array Experimental eye research Medium 31586450

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology. Endocrinology 293 22495674
2009 GPR30/GPER1: searching for a role in estrogen physiology. Trends in endocrinology and metabolism: TEM 186 19734054
2015 Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1. Journal of leukocyte biology 148 26394816
2017 GPER1/GPR30 in the brain: Crosstalk with classical estrogen receptors and implications for behavior. The Journal of steroid biochemistry and molecular biology 89 28465157
2013 GPER-1 acts as a tumor suppressor in ovarian cancer. Journal of ovarian research 86 23849542
2015 Contribution of estrogen receptor subtypes, ERα, ERβ, and GPER1 in rapid estradiol-mediated enhancement of hippocampal synaptic transmission in mice. Hippocampus 81 25980457
2011 G protein-coupled oestrogen receptor 1 (GPER1)/GPR30: a new player in cardiovascular and metabolic oestrogenic signalling. British journal of pharmacology 75 21250980
2016 Emerging roles for the novel estrogen-sensing receptor GPER1 in the CNS. Neuropharmacology 68 27392633
2015 A novel form of synaptic plasticity in field CA3 of hippocampus requires GPER1 activation and BDNF release. The Journal of cell biology 60 26391661
2011 The GPER1 agonist G-1 attenuates endothelial cell proliferation by inhibiting DNA synthesis and accumulating cells in the S and G2 phases of the cell cycle. Journal of vascular research 60 21273787
2014 GPER-1 and estrogen receptor-β ligands modulate aldosterone synthesis. Endocrinology 57 25167221
2017 The Glycolytic Enzyme PFKFB3 Is Involved in Estrogen-Mediated Angiogenesis via GPER1. The Journal of pharmacology and experimental therapeutics 56 28348059
2019 Stabilization of MORC2 by estrogen and antiestrogens through GPER1- PRKACA-CMA pathway contributes to estrogen-induced proliferation and endocrine resistance of breast cancer cells. Autophagy 55 32401166
2016 Activation of G protein-coupled estrogen receptor 1 (GPER-1) ameliorates blood-brain barrier permeability after global cerebral ischemia in ovariectomized rats. Biochemical and biophysical research communications 54 27311857
2014 Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis. PloS one 54 24736568
2014 GPER1 (GPR30) knockout mice display reduced anxiety and altered stress response in a sex and paradigm dependent manner. Hormones and behavior 54 25236887
2018 Attenuation of Microbiotal Dysbiosis and Hypertension in a CRISPR/Cas9 Gene Ablation Rat Model of GPER1. Hypertension (Dallas, Tex. : 1979) 51 30354811
2021 GPER1 is required to protect fetal health from maternal inflammation. Science (New York, N.Y.) 50 33446553
2012 Implication of GPER1 in neuroprotection in a mouse model of Parkinson's disease. Neurobiology of aging 48 22749492
2012 GPER1/GPR30 activation improves neuronal survival following global cerebral ischemia induced by cardiac arrest in mice. Translational stroke research 48 23483801
2015 Prunetin signals via G-protein-coupled receptor, GPR30(GPER1): Stimulation of adenylyl cyclase and cAMP-mediated activation of MAPK signaling induces Runx2 expression in osteoblasts to promote bone regeneration. The Journal of nutritional biochemistry 47 26345541
2017 G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms. The Journal of biological chemistry 46 28450397
2015 GPER1-mediated immunomodulation and neuroprotection in the myenteric plexus of a mouse model of Parkinson's disease. Neurobiology of disease 46 26051538
2013 GPER-1 expression decreases during breast cancer tumorigenesis. Cancer investigation 44 23688258
2014 Ceramide synthases CerS4 and CerS5 are upregulated by 17β-estradiol and GPER1 via AP-1 in human breast cancer cells. Biochemical pharmacology 41 25451689
2018 G-protein-coupled estrogen receptor GPER-1 expression in hormone receptor-positive breast cancer is associated with poor benefit of tamoxifen. Breast cancer research and treatment 40 30478785
2020 GPER1 Silencing Suppresses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Inhibiting PI3K/AKT-Mediated EMT. Frontiers in cell and developmental biology 39 33425895
2014 GPER1 is regulated by insulin in cancer cells and cancer-associated fibroblasts. Endocrine-related cancer 38 25012984
2020 Continuous Exposure of Breast Cancer Cells to Tamoxifen Upregulates GPER-1 and Increases Cell Proliferation. Frontiers in endocrinology 37 33117280
2014 High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma. International journal of clinical and experimental pathology 35 25031742
2013 17β-estradiol promotes the invasion and migration of nuclear estrogen receptor-negative breast cancer cells through cross-talk between GPER1 and CXCR1. The Journal of steroid biochemistry and molecular biology 35 23907016
2013 GPCR-mediated rapid, non-genomic actions of steroids: comparisons between DmDopEcR and GPER1 (GPR30). General and comparative endocrinology 32 24188886
2011 Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells. Frontiers in bioscience (Landmark edition) 32 21196169
2016 Characterisation of Signalling by the Endogenous GPER1 (GPR30) Receptor in an Embryonic Mouse Hippocampal Cell Line (mHippoE-18). PloS one 31 26998610
2018 Low-concentration BPF induced cell biological responses by the ERα and GPER1-mediated signaling pathways in MCF-7 breast cancer cells. Ecotoxicology and environmental safety 30 30195206
2016 GPER1 mediates estrogen-induced neuroprotection against oxygen-glucose deprivation in the primary hippocampal neurons. Neuroscience 30 27113328
2019 A Novel Mechanism of S-equol Action in Neurons and Astrocytes: The Possible Involvement of GPR30/GPER1. International journal of molecular sciences 29 31635400
2018 Is the membrane estrogen receptor, GPER1, a promiscuous receptor that modulates nuclear estrogen receptor-mediated functions in the brain? Hormones and behavior 29 29964007
2017 Depressive-like effect of prenatal exposure to DDT involves global DNA hypomethylation and impairment of GPER1/ESR1 protein levels but not ESR2 and AHR/ARNT signaling. The Journal of steroid biochemistry and molecular biology 28 28263910
2019 Autocrine motility factor promotes endometrial cancer progression by targeting GPER-1. Cell communication and signaling : CCS 26 30836961
2019 Sequential ligand- and structure-based virtual screening approach for the identification of potential G protein-coupled estrogen receptor-1 (GPER-1) modulators. RSC advances 25 35520492
2018 Shenmai injection improves the postoperative immune function of papillary thyroid carcinoma patients by inhibiting differentiation into Treg cells via miR-103/GPER1 axis. Drug development research 25 30267584
2013 Vasoconstriction induced by G1, a G-protein-coupled oestrogen receptor1 (GPER-1) agonist, in the isolated perfused rat kidney. European journal of pharmacology 25 23376418
2018 Role of estrogens in fish immunity with special emphasis on GPER1. Developmental and comparative immunology 24 30092317
2016 Understanding the molecular basis of agonist/antagonist mechanism of GPER1/GPR30 through structural and energetic analyses. The Journal of steroid biochemistry and molecular biology 24 26772481
2015 17β-estradiol inhibits spreading of metastatic cells from granulosa cell tumors through a non-genomic mechanism involving GPER1. Carcinogenesis 24 25823895
2020 G Protein-Coupled Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive Diseases. Frontiers in endocrinology 23 33281743
2019 The neuroprotective effects of novel estrogen receptor GPER1 in mouse retinal ganglion cell degeneration. Experimental eye research 23 31586450
2013 The G protein-coupled estrogen receptor 1 (GPER1/GPR30) agonist G-1 regulates vascular smooth muscle cell Ca²⁺ handling. Journal of vascular research 23 24080531
2018 Oestrogen Inhibits VEGF Expression And Angiogenesis In Triple-Negative Breast Cancer By Activating GPER-1. Journal of Cancer 22 30405852
2016 Serum levels of G protein-coupled estrogen receptor 1 (GPER1) in drug-naive patients with generalized anxiety disorder. Psychiatry research 22 27512921
2014 Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway. International journal of molecular medicine 22 24718680
2013 GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth factor receptor-dependent signalling pathway. The Journal of pharmacy and pharmacology 22 24028616
2020 G protein-coupled estrogen receptor 1 (GPER-1) and agonist G-1 inhibit growth of ovarian cancer cells by activation of anti-tumoral transcriptome responses: impact of GPER-1 mRNA on survival. Journal of cancer research and clinical oncology 21 32813115
2017 Hyper-methylation of the upstream CpG island shore is a likely mechanism of GPER1 silencing in breast cancer cells. Gene 21 28286086
2016 The protective role of G protein-coupled estrogen receptor 1 (GPER-1) on methotrexate-induced nephrotoxicity in human renal epithelium cells. Renal failure 21 26981789
2014 The G protein-coupled estrogen receptor-1, GPER-1, promotes fibrillogenesis via a Shc-dependent pathway resulting in anchorage-independent growth. Hormones & cancer 21 25096985
2021 Bazi Bushen Capsule Alleviates Post-Menopausal Atherosclerosis via GPER1-Dependent Anti-Inflammatory and Anti-Apoptotic Effects. Frontiers in pharmacology 20 34248622
2021 ERα36-GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells. International journal of molecular sciences 20 34299224
2015 Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats. Hormones and behavior 20 26093261
2015 Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells. Oncology letters 20 26722308
2021 Saikosaponin-d alleviates hepatic fibrosis through regulating GPER1/autophagy signaling. Molecular biology reports 19 34714484
2020 GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients. Archives of gynecology and obstetrics 19 31900584
2020 Does GPER1 Play a Role in Sexual Dimorphism? Frontiers in endocrinology 17 33193108
2019 GPER1 influences cellular homeostasis and cytostatic drug resistance via influencing long chain ceramide synthesis in breast cancer cells. The international journal of biochemistry & cell biology 17 31082617
2020 The G protein-coupled oestrogen receptor, GPER1, mediates direct anti-inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert. Journal of neuroendocrinology 16 32077170
2020 The GPER1/SPOP axis mediates ubiquitination-dependent degradation of ERα to inhibit the growth of breast cancer induced by oestrogen. Cancer letters 16 33069770
2019 Targeting GPER1 to suppress autophagy as a male-specific therapeutic strategy for iron-induced striatal injury. Scientific reports 16 31040364
2018 Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats. Hormones and behavior 16 29807036
2020 The novel estrogen receptor GPER1 decreases epilepsy severity and susceptivity in the hippocampus after status epilepticus. Neuroscience letters 15 32302699
2019 Environmental polycyclic aromatic hydrocarbons mixture, in human blood levels, decreased oestradiol secretion by granulosa cells via ESR1 and GPER1 but not ESR2 receptor. Human & experimental toxicology 15 31698960
2014 GPER1 stimulation alters posttranslational modification of RGSz1 and induces desensitization of 5-HT1A receptor signaling in the rat hypothalamus. Neuroendocrinology 15 25402859
2022 Bisphenol F blocks Leydig cell maturation and steroidogenesis in pubertal male rats through suppressing androgen receptor signaling and activating G-protein coupled estrogen receptor 1 (GPER1) signaling. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 14 35803362
2022 Suppression of G Protein-coupled Estrogen Receptor 1 (GPER1) Enhances the Anti-invasive Efficacy of Selective ERβ Agonists. Anticancer research 14 36288854
2020 Chronic GPER1 Activation Protects Against Oxidative Stress-Induced Cardiomyoblast Death via Preservation of Mitochondrial Integrity and Deactivation of Mammalian Sterile-20-Like Kinase/Yes-Associated Protein Pathway. Frontiers in endocrinology 14 33193095
2015 GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells. Molecular and cellular endocrinology 14 26690777
2023 Knockdown of G Protein-coupled Estrogen Receptor 1 (GPER1) Enhances Tumor-supportive Properties in Cervical Carcinoma Cells. Cancer genomics & proteomics 13 37093686
2020 MiR-155-Mediated Deregulation of GPER1 Plays an Important Role in the Gender Differences Related to Inflammatory Bowel Disease. The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale 13 33014211
2023 Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta. Journal of pineal research 12 37746893
2023 Activation of GPER1 in macrophages ameliorates UUO-induced renal fibrosis. Cell death & disease 12 38086848
2022 Changes in expression of signal transduction-related genes, and formation of aggregates of GPER1 and OXTR receptors in mucopolysaccharidosis cells. European journal of cell biology 12 35537249
2018 Serum levels of GPER-1 in euthymic bipolar patients. Neuropsychiatric disease and treatment 11 29618927
2017 Oxabicycloheptene Sulfonate Protects Against β-Amyloid-induced Toxicity by Activation of PI3K/Akt and ERK Signaling Pathways Via GPER1 in C6 Cells. Neurochemical research 11 28374135
2017 GPER1 in sand rat epididymis: Effects of seasonal variations, castration and efferent ducts ligation. Animal reproduction science 11 28688795
2016 Homology Modeling, Validation and Dynamics of the G Protein-coupled Estrogen Receptor 1 (GPER-1). Molecular informatics 11 27546037
2013 G protein-coupled estrogen receptor1 (GPER1) may mediate Rho-kinase (ROCK-2) up-regulation in coronary endothelial cells. Endocrine regulations 11 23641788
2024 Activation of GPER-1 Attenuates Traumatic Brain Injury-Induced Neurological Impairments in Mice. Molecular neurobiology 10 38217667
2024 Activation of GPER1 by G1 prevents PTSD-like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection. CNS neuroscience & therapeutics 10 38992889
2022 Bisphenol S induces Agrp expression through GPER1 activation and alters transcription factor expression in immortalized hypothalamic neurons: A mechanism distinct from BPA-induced upregulation. Molecular and cellular endocrinology 10 35569583
2018 Lordosis facilitated by GPER-1 receptor activation involves GnRH-1, progestin and estrogen receptors in estrogen-primed rats. Hormones and behavior 10 29269179
2018 Selection of a GPER1 Ligand via Ligand-based Virtual Screening Coupled to Molecular Dynamics Simulations and Its Anti-proliferative Effects on Breast Cancer Cells. Anti-cancer agents in medicinal chemistry 10 29745344
2024 Selenium restored mitophagic flux to alleviate cadmium-induced hepatotoxicity by inhibiting excessive GPER1-mediated mitophagy activation. Journal of hazardous materials 9 38880044
2023 GPER1 Activation Exerts Anti-Tumor Activity in Multiple Myeloma. Cells 9 37759449
2022 Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells. Molecular and cellular endocrinology 9 36096380
2022 The Interplay of GPER1 with 17β-Aminoestrogens in the Regulation of the Proliferation of Cervical and Breast Cancer Cells: A Pharmacological Approach. International journal of environmental research and public health 9 36231664
2022 Multiplex G Protein-Coupled Receptor Screen Reveals Reliably Acting Agonists and a Gq-Phospholipase C Coupling Mode of GPR30/GPER1. Molecular pharmacology 9 36400433
2020 GPER1 and microRNA: Two Players in Breast Cancer Progression. International journal of molecular sciences 9 33374170
2019 Effects of the selective GPER1 agonist G1 on bone growth. Endocrine connections 9 31434056
2019 GPER1 in the thyroid: A systematic review. Life sciences 9 31790688
2015 Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma. International journal of clinical and experimental pathology 9 26617848