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Showing GPER1 — GPR30 is a alias.

GPER1

G-protein coupled estrogen receptor 1 · UniProt Q99527

Length
375 aa
Mass
42.2 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPER1 (GPR30) is a seven-transmembrane G protein-coupled estrogen receptor that translates estrogen binding into rapid non-genomic signaling to regulate vascular, neuronal, reproductive, immune, and oncogenic processes (PMID:22495674, PMID:33446553). As a Gs-coupled receptor it stimulates adenylyl cyclase and drives Gβγ-dependent release of membrane-tethered HB-EGF, transactivating the EGFR (PMID:22495674); in parallel it engages Gi/o to increase ERK1/2 activity through both a constitutive PDZ-motif/AKAP5-anchored mechanism and a ligand-stimulated PDZ-independent mechanism, with the PDZ interaction (SAP97, AKAP5) anchoring the receptor at the plasma membrane and constitutively lowering cAMP (PMID:28450397), and it couples to a Gq–phospholipase C–PKC–ERK cascade whose prominence tracks with cell-type-specific plasma-membrane versus endomembrane localization (PMID:36400433). Downstream, GPER1 signals through PKA, PI3K/Akt, and MAPK/ERK to diverse effectors: it activates PRKACA to phosphorylate MORC2 at Thr582, blocking its chaperone-mediated autophagic degradation (PMID:32401166), and upregulates the Cullin3 E3 ligase adaptor SPOP to drive ubiquitin-proteasomal degradation of ERα, restraining estrogen-driven breast cancer growth (PMID:33069770). In the nervous system it triggers hippocampal BDNF release with Arc translation and AMPA-receptor (GluA1) internalization underlying synaptic plasticity (PMID:26391661) and mediates estradiol-induced potentiation of CA3–CA1 transmission via ERK (PMID:25980457). In the vasculature it controls tone through EGFR/Src/Akt-dependent vasorelaxation and L-type Ca2+ channel inhibition in smooth muscle (PMID:24028616, PMID:24080531). GPER1 also suppresses inflammatory signaling—co-regulating NF-κB with ERα36 and interacting with p65 (PMID:34299224, PMID:26394816)—and, genetically, is a required suppressor of type I interferon signaling protecting fetal development under maternal inflammation (PMID:33446553). Additional aldosterone, angiogenic, and matrix-assembly roles connect the receptor to adrenocortical PKA signaling, glycolytic PFKFB3, and integrin α5β1–Shc adhesion complexes (PMID:25167221, PMID:28348059, PMID:25096985).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2012 High

    Established that GPER1 is a bona fide membrane estrogen receptor pharmacologically distinct from nuclear ERs, defining its core Gs/cAMP and EGFR-transactivation output.

    Evidence Pharmacological agonist/antagonist dissection, receptor knockdown, and cAMP assays

    PMID:22495674

    Open questions at the time
    • Did not resolve which G proteins dominate in different cell types
    • No structural basis for ligand discrimination
  2. 2017 High

    Resolved how GPER1 controls ERK1/2, distinguishing a constitutive PDZ/AKAP5-anchored route from a ligand-stimulated PDZ-independent route and linking receptor anchoring to cAMP regulation.

    Evidence PDZ-motif deletion mutants, AKAP5 knockdown, pertussis toxin and kinase/phosphatase inhibitors with ERK1/2 assays

    PMID:28450397

    Open questions at the time
    • Physiological relevance of constitutive vs. ligand-driven signaling in vivo not defined
    • Whether the two mechanisms act in the same cells unclear
  3. 2022 High

    Demonstrated Gq–PLC–PKC–ERK coupling and showed that subcellular localization (plasma membrane vs. endomembrane) reconciles contradictory signaling reports across cell lines.

    Evidence Multiplexed GPCR Ca2+ screen, Gq inhibitor YM-254890, internalization and localization imaging across multiple cell lines

    PMID:36400433

    Open questions at the time
    • Failure to reproduce cAMP increases leaves Gs coupling context-dependent and unresolved
    • Determinants of plasma-membrane versus endomembrane targeting unidentified
  4. 2015 High

    Connected GPER1 to synaptic plasticity by showing it drives BDNF release, Arc translation, and AMPA receptor internalization, providing a mechanism for estrogen modulation of hippocampal function.

    Evidence GPER1 agonist G1, BDNF/Arc/GluA1 assays, proteasome inhibition, and hippocampal slice electrophysiology

    PMID:25980457 PMID:26391661

    Open questions at the time
    • Endogenous estrogen ligand source in this circuit not established
    • Receptor localization (pre- vs. postsynaptic) not defined
  5. 2019 High

    Identified a GPER1→PRKACA→MORC2 phosphorylation axis that stabilizes MORC2 by blocking chaperone-mediated autophagy, linking the receptor to antiestrogen resistance.

    Evidence Co-IP, T582A phospho-site mutagenesis, CMA pathway inhibition, and knockdown/rescue in breast cancer cells

    PMID:32401166

    Open questions at the time
    • Direct kinase–substrate contact not structurally resolved
    • Generality beyond breast cancer cells untested
  6. 2020 High

    Showed GPER1 negatively regulates ERα protein via SPOP-mediated ubiquitin-proteasomal degradation, establishing a tumor-suppressive cross-talk with the nuclear estrogen pathway.

    Evidence Co-IP, ubiquitination assay, SPOP knockdown rescue, proteasome inhibition, and xenograft validation

    PMID:33069770

    Open questions at the time
    • Signaling steps linking GPER1 activation to SPOP upregulation not mapped
    • Whether SPOP induction is transcriptional or post-translational unclear
  7. 2021 High

    Genetic knockout established GPER1 as a necessary suppressor of type I interferon signaling that protects fetal development during maternal inflammation.

    Evidence GPER1 knockout mice, maternal inflammation models, and tissue-specific IFN signaling comparison

    PMID:33446553

    Open questions at the time
    • Molecular link between GPER1 and IFN pathway components not defined
    • Cell type mediating tissue-selective suppression unidentified
  8. 2014 Medium

    Extended GPER1 outputs to steroidogenesis and matrix biology, showing PKA-driven aldosterone synthase induction and integrin α5β1–Shc–dependent fibronectin assembly.

    Evidence Agonist/antagonist plus gene silencing for aldosterone (HAC15 cells) and Shc Y317F mutagenesis with adhesion/haptotaxis assays

    PMID:25096985 PMID:25167221

    Open questions at the time
    • Single-lab findings for each role
    • Interplay with ERβ in steroidogenic regulation only partially mapped
  9. 2013 Medium

    Defined GPER1 control of vascular tone through EGFR/Src/Akt-dependent vasorelaxation and L-type Ca2+ channel inhibition in smooth muscle.

    Evidence Ex vivo aortic/renal preparations and A7r5 Ca2+ imaging with selective kinase and channel inhibitors plus GPER1 antagonists

    PMID:23376418 PMID:24028616 PMID:24080531

    Open questions at the time
    • Pharmacology-only dissection without genetic confirmation in vessels
    • Reconciliation of vasoconstrictor versus vasodilator effects across beds incomplete
  10. 2020 Medium

    Implicated GPER1 in inflammatory suppression via physical partnership with ERα36 and direct interaction with NF-κB p65 to inhibit TLR4-driven cytokine production.

    Evidence Co-IP of GPER1 with ERα36 and p65, siRNA knockdown, and NF-κB reporter/cytokine assays in breast cancer cells and monocytes

    PMID:26394816 PMID:34299224

    Open questions at the time
    • Reciprocal/structural validation of the GPER1–p65 interaction lacking
    • Whether GPER1 acts at the membrane or nucleus in this complex unclear
  11. 2019 Medium

    Identified autocrine motility factor as a direct GPER1-binding partner that co-translocates and activates PI3K/AKT to promote cancer cell growth.

    Evidence Yeast two-hybrid, Co-IP, immunofluorescence, iTRAQ proteomics, and xenograft model in endometrial cancer cells

    PMID:30836961

    Open questions at the time
    • Binding interface and stoichiometry undefined
    • Physiological relevance outside cancer context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How cell-type-specific localization and ligand identity dictate the choice among Gs, Gi/o, and Gq outputs, and the structural basis of GPER1 ligand recognition, remain unresolved.
  • No structural model of ligand-bound GPER1 in the corpus
  • Determinants of plasma-membrane vs. endomembrane retention unknown
  • In vivo dominance of each G-protein pathway not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2
Partners
AKAP5AMFEGFRERA36RELASAP97

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 GPER-1 (GPR30) is a Gs-coupled heptahelical transmembrane receptor that stimulates adenylyl cyclase and promotes Gβγ-subunit protein-dependent release of membrane-tethered heparan-bound epidermal growth factor (HB-EGF); selective agonists/antagonists discriminate it from nuclear ERα and ERβ. Pharmacological agonist/antagonist studies, receptor knockdown, cAMP assays Endocrinology High 22495674
2017 GPR30/GPER1 increases ERK1/2 activity via two distinct Gi/o-mediated mechanisms: (1) a PDZ motif-dependent constitutive mechanism requiring AKAP5, and (2) a PDZ-independent G-1-stimulated mechanism; the PDZ interaction with SAP97 and AKAP5 anchors the receptor at the plasma membrane and also mediates a constitutive decrease in cAMP independently of Gi/o. PDZ motif deletion mutants, AKAP5 knockdown, pertussis toxin (Gi/o inhibitor), PI3K inhibitor wortmannin, EGFR inhibitor AG1478, phosphatase inhibitors FK506 and okadaic acid; ERK1/2 activity assays The Journal of biological chemistry High 28450397
2022 GPR30/GPER1 couples to the canonical Gq-phospholipase C pathway, activating protein kinase C and ERK; the receptor undergoes internalization upon continuous agonist exposure. Cell-line-dependent localization (plasma membrane in HEK293 and MCF-7; endomembrane retention in Cos-7 and HeLa) explains conflicting signaling reports. Classical agonists (17β-estradiol, 4-OHT, G-1) did not reproduce cAMP increases in this system. Multiplexed GPCR Ca2+ screen, stable/transient overexpression in HEK293 and multiple cell lines, Gq inhibitor YM-254890, PLC and PKC pathway analysis, receptor internalization assay, fluorescent fusion protein imaging Molecular pharmacology High 36400433
2019 GPER1 activates PRKACA (protein kinase A catalytic subunit alpha), which phosphorylates MORC2 at threonine 582; phosphorylated MORC2 reduces its interaction with HSPA8 and LAMP2A (chaperone-mediated autophagy components), protecting MORC2 from lysosomal degradation. A phosphorylation-lacking MORC2 T582A mutant cannot restore antiestrogen resistance. Co-immunoprecipitation, phosphorylation-site mutagenesis (T582A), CMA pathway inhibition, GPER1-dependent PRKACA activation assays, knockdown and rescue experiments in breast cancer cells Autophagy High 32401166
2015 GPER1 activation triggers BDNF release in hippocampal field CA3, leading to transient stimulation of Arc protein translation and GluA1-containing AMPA receptor internalization; mGluR-dependent LTD at the mossy fiber pathway requires prior GPER1 stimulation and is associated with ubiquitin-proteasome-mediated degradation of GluA1. Selective GPER1 agonist G1, BDNF release assay, Arc translation assay, GluA1 internalization assay, proteasome inhibition, live hippocampal slice electrophysiology The Journal of cell biology High 26391661
2014 GPER-1 stimulation with selective agonist G-1 increases aldosterone synthase expression and aldosterone production via protein kinase A signaling in adrenocortical HAC15 cells; silencing of ERβ unmasks this stimulatory GPER-1 effect, while silencing of GPER-1 blunts aldosterone synthase expression and blocks E2-stimulated aldosterone production under ERβ blockade. GPER-1 agonist G-1, GPER-1 antagonist G-15, selective PKA inhibitor, gene silencing (ERβ and GPER-1 siRNA), aldosterone synthase expression assays, aldosterone production measurement Endocrinology High 25167221
2020 GPER1 negatively regulates ERα protein levels by upregulating the Cullin3-based E3 ubiquitin ligase adaptor SPOP, which promotes ubiquitin-proteasome-dependent degradation of ERα; SPOP depletion abrogates GPER1-induced ERα ubiquitination and degradation. GPER1 activation inhibits E2-induced ERα+ breast cancer cell proliferation in vitro and tumor growth in vivo. Co-immunoprecipitation, ubiquitination assay, SPOP knockdown rescue experiments, proteasome inhibition, in vivo xenograft model Cancer letters High 33069770
2014 GPER-1 promotes fibronectin (FN) matrix assembly and release of HB-EGF; GPER-1 stimulation forms integrin α5β1-Shc adaptor protein complexes at fibrillar adhesions. Shc mutant Y317F (lacking primary tyrosyl phosphorylation site) disrupts E2-induced focal adhesion and actin stress fiber formation and abolishes E2-enhanced haptotaxis and FN-dependent anchorage-independent growth. Stable Shc Y317F mutant expression, focal adhesion and actin stress fiber imaging, haptotaxis assays, hanging-drop anchorage-independent growth assay, immunoprecipitation of integrin α5β1-Shc complexes Hormones & cancer Medium 25096985
2017 Estrogen-induced angiogenesis via GPER1 requires upregulation of the glycolytic enzyme PFKFB3 in HUVECs; GPER1 antagonist G-15 or GPER1 siRNA abolishes E2-induced PFKFB3 expression, and PFKFB3 inhibition blocks GPER1-mediated HUVEC migration. GPER1-selective agonist G-1, GPER1 antagonist G-15, GPER1 siRNA, PFKFB3 inhibitor, HUVEC migration and angiogenesis assays, PFKFB3 expression measurement The Journal of pharmacology and experimental therapeutics Medium 28348059
2013 GPER-1-mediated vasoconstriction in isolated rat kidney involves ROCK, PKC, p38 MAPK, p42/44 MAPK, tyrosine kinase, EGF receptor kinase and voltage-operated Ca2+ channels but not JNK or PI3K; the effect is endothelium-independent and blocked by GPER-1 antagonist G15. Isolated perfused rat kidney, selective kinase inhibitors (Y-27632 for ROCK, PD98059 for ERK, SB203580 for p38, GF109203X for PKC, genistein for tyrosine kinase, AG-1478 for EGFR, nifedipine for Ca2+ channels), endothelium removal with saponin, Western blot for GPER-1 expression European journal of pharmacology Medium 23376418
2013 GPER-1 agonist G1 induces endothelium-dependent vasorelaxation via Src-mediated transactivation of the EGF receptor, followed by Akt pathway activation; this is blocked by NOS inhibitor L-NAME, EGFR blockers AG1478 and DAPH, Src inhibitor, and Akt inhibitor VIII, but not by classical ER antagonists, PI3K inhibitors or ERK inhibitor. Rat aortic ring organ bath experiments, selective inhibitors of NOS, EGFR, Src, Akt, PI3K, ERK; GPER-1 antagonist HB-EGF The Journal of pharmacy and pharmacology Medium 24028616
2013 GPER-1 agonist G1 reduces vascular smooth muscle cell Ca2+ spike activity by blocking voltage-sensitive L-type Ca2+ channels; the effect is blocked by GPER-1 antagonist G15, supporting a GPER-1-dependent mechanism for blood pressure regulation. Ca2+ imaging in A7r5 smooth muscle cells, L-type Ca2+ channel blocker nifedipine, GPER-1 antagonist G15, thromboxane A2 analogue stimulation, KCl-evoked Ca2+ measurement Journal of vascular research Medium 24080531
2013 GPER1 activation via G1 upregulates ROCK-2 expression in rat coronary vascular endothelial cells through GPER1 and EGFR transactivation; the effect requires Gi/o protein signaling (blocked by pertussis toxin), EGFR kinase (blocked by AG-1478), and de novo transcription (blocked by actinomycin-D), but is not replicated by ERα or ERβ selective agonists. Western blot for ROCK-2 and GPER1 in primary rat coronary vascular endothelial cells, GPER1 agonist G1, GPER1 antagonist G-15, pertussis toxin (Gi/o inhibitor), AG-1478 (EGFR blocker), actinomycin-D (transcription inhibitor), ERα/ERβ agonists Endocrine regulations Low 23641788
2014 GPER1 stimulation of 5-HT1A receptor desensitization in the rat hypothalamic paraventricular nucleus involves altered isoform expression and posttranslational modification of RGSz1; high-molecular-weight SUMOylated and glycosylated RGSz1 is increased by G-1 treatment and localizes to the detergent-resistant membrane microdomain, where it can reduce Gαz activity and uncouple 5-HT1AR signaling. Selective GPER1 agonist G-1, subcellular fractionation (detergent-resistant microdomains), Western blot for RGSz1 isoforms, SUMO and glycosylation analysis, oxytocin/ACTH hormonal response assays in vivo Neuroendocrinology Medium 25402859
2021 GPER1 activation during pregnancy suppresses interferon (IFN) signaling preferentially in reproductive and fetal tissues; GPER1 inactivation in mice caused fetal demise and halted fetal development only in the context of maternal inflammation, establishing GPER1 as a necessary regulator of type I IFN signaling that protects fetal health. GPER1 knockout mice, maternal inflammation models, IFN signaling assays in fetal vs. maternal tissues, tissue-specific comparison of IFN suppression Science (New York, N.Y.) High 33446553
2015 GPER1 activation by 17β-estradiol inhibits constitutively active ERK1/2 in granulosa cell tumor cells and decreases migration and matrix invasion through non-genomic mechanisms; this anti-metastatic effect is mediated specifically by GPER1 signaling as demonstrated by pharmacological and RNA silencing approaches. Pharmacological GPER1 inhibitors, siRNA silencing of GPER1, ERK1/2 phosphorylation assays, migration and matrix invasion assays in KGN and COV434 cells Carcinogenesis Medium 25823895
2014 GPER-1 activation by E2 or selective agonist G-1 downregulates testosterone production in LH-stimulated isolated rat Leydig cells and in human testicular tissue by 20-30%; this is a GPER-1-specific effect as the testis lacks ERα. Isolated rat Leydig cells and human testis tissue, selective GPER-1 agonist G-1, ERα/β antagonist ICI 182,780, radioimmunoassay of testosterone, qRT-PCR and immunofluorescence for GPER-1 localization, MTS cell viability assay PloS one Medium 24736568
2019 Autocrine motility factor (AMF) physically binds to GPER-1, and the AMF-GPER-1 complex translocates from the plasma membrane to the cytoplasm; this interaction triggers PI3K/AKT signaling to promote endometrial cancer cell growth. Yeast two-hybrid assay, co-immunoprecipitation, immunofluorescence, iTRAQ proteomic analysis of downstream pathway, xenograft mouse model Cell communication and signaling : CCS Medium 30836961
2015 GPER1 mediates estradiol-induced enhancement of hippocampal CA3-CA1 synaptic transmission; G1 pretreatment occludes EB-mediated enhancement, GPER1 antagonist G15 blocks EB-induced synaptic enhancement, and the effect requires ERK activation regardless of ERα or ERβ genotype. Extracellular field potential recordings in hippocampal slices from WT, ERαKO, and ERβKO mice; selective GPER1 agonist G1, antagonist G15, ERK inhibitor, occlusion experiments Hippocampus Medium 25980457
2016 In embryonic hippocampal mHippoE-18 cells, GPER1 activation by 17β-estradiol, G1, tamoxifen, or ICI 182,780 produces dose-dependent potentiation of forskolin-stimulated cAMP (not observed with ERα or ERβ agonists); however, GPER1-specific antagonists G15 and G36 convert agonist-induced cAMP stimulation into inhibition, while aldosterone mimics the antagonist-induced inhibitory effect — consistent with 'biased antagonism' altering receptor coupling. cAMP assay in mHippoE-18 cells (endogenous GPER1), selective ER agonists (PPT for ERα, DPN for ERβ), GPER1 antagonists G15 and G36, aldosterone treatment PloS one Medium 26998610
2014 Insulin transactivates the GPER1 promoter and increases GPER1 mRNA and protein expression through the PRKCD/MAPK1/c-Fos/AP1 transduction pathway in leiomyosarcoma cells and breast cancer-associated fibroblasts; GPER1-dependent cell migration triggered by insulin occurs through GPER1 and its target gene CTGF. GPER1 promoter reporter assay, pharmacological inhibitors of PRKCD and MAPK1, gene silencing, cell migration assays Endocrine-related cancer Medium 25012984
2015 In breast cancer cells, 17β-estradiol and GPER1 upregulate ceramide synthases CerS4 and CerS5 via AP-1 transcription factor activation (most likely through dimerization of c-Jun and c-Fos); GPER1 co-transfection enhances CerS2, CerS4, and CerS6 promoter activity. Luciferase reporter gene assays with CerS promoter constructs, promoter deletion and mutation analysis, co-transfection of GPER1, fulvestrant inhibition Biochemical pharmacology Medium 25451689
2015 GPER1 activation in MCF-7 breast cancer cells mediates 4-OHT (tamoxifen)-induced IGFBP-1 transcription via CREB; extracellular IGFBP-1 then inhibits IGF-1-dependent PI3K/Akt signaling. GPER1 knockdown abrogates 4-OHT-dependent IGFBP-1 induction. Conditioned medium transfer experiments, IGFBP-1 mRNA and protein measurement, GPER1 knockdown, CREB knockdown, phospho-Akt assay, neutralizing antibody experiments Molecular and cellular endocrinology Medium 26690777
2016 GPER-1 activation reduces BBB permeability after global cerebral ischemia by increasing tight junction proteins (occludin and claudin-5) and decreasing VEGF-A expression in the CA1 region. Intracerebroventricular GPER-1 agonist G1 injection in 4-vessel occlusion rat model, IgG extravasation assay, Western blot for tight junctions and VEGF-A Biochemical and biophysical research communications Low 27311857
2011 GPER1 agonist G-1 attenuates endothelial cell proliferation by inhibiting DNA synthesis and accumulating cells in S and G2 phases; GPER1 siRNA prevents G-1-induced attenuation of DNA synthesis, confirming GPER1 dependence. The antiproliferative effect is independent of ERK/MAP kinase. GPER1 siRNA in bEnd.3 cells, BrdU/DNA synthesis assay, cell cycle analysis, ERK inhibitor PD98059, comparison in COS-7 cells (low GPER1 expression) Journal of vascular research Medium 21273787
2017 GPER1 knockdown in gastric cancer cells suppresses proliferation, migration, and invasion by inhibiting PI3K/AKT-mediated EMT; PI3K activator 740Y-P reverses these effects, placing GPER1 upstream of PI3K/AKT in this pathway. siRNA knockdown of GPER1, PI3K activator rescue experiment, EMT marker expression (E-cadherin, N-cadherin, vimentin), transcription factor analysis (Snail, Slug, Twist1), GPER1 overexpression plasmid Frontiers in cell and developmental biology Medium 33425895
2016 GPER1 mediates neuroprotection against oxygen-glucose deprivation in hippocampal neurons via PI3K/Akt-dependent Ask1 inhibition; GPER1 knockdown diminishes E2/E2-BSA protection, while GPER1 overexpression potentiates it. GPER1 knockdown and overexpression in primary hippocampal neurons, OGD model, membrane-impermeable E2-BSA, PI3K inhibition, Ask1 phosphorylation assay Neuroscience Medium 27113328
2020 ERα36 and GPER1 physically interact (by Co-IP) and collaborate to inhibit LPS/TLR4-induced NF-κB activity; GPER1 directly interacts with the p65 component of NF-κB in breast cancer cells. ERα36 knockdown partially inhibits this anti-inflammatory effect in the presence of ERα66. Co-immunoprecipitation of ERα36 with GPER1 and with NF-κB p65, siRNA knockdown, NF-κB reporter assay, IL-6/TNFα expression International journal of molecular sciences Medium 34299224
2015 In human monocytes, GPER1 physically interacts with ERα36 splice variant; ligand-activated ERα36 directly interacts with the p65 component of NF-κB in the nucleus to inhibit IL-6 expression. GPER1 acts as a co-regulator—its inhibition blocks estrogen's anti-IL-6 effect, but GPER1 activation alone does not mimic it. Co-immunoprecipitation of GPER1 with ERα36, nuclear interaction of ERα36 with p65 NF-κB, GPER1/ERα36 selective inhibitors, IL-6 measurement, NF-κB reporter assay in primary human monocytes Journal of leukocyte biology Medium 26394816
2019 GPER1 agonist G-1 activates BDNF/TrkB signaling in the hippocampus to improve synaptic and mitochondrial function in SPS (PTSD model) mice; the effect is blocked by both GPER1 antagonist G15 and TrkB inhibitor ANA-12, placing GPER1 upstream of BDNF/TrkB. Western blot and immunofluorescence for GPER1, BDNF/TrkB pathway analysis, electrophysiological LFP recordings, synaptic and mitochondrial protein expression, GPER1 agonist/antagonist in SPS mouse model CNS neuroscience & therapeutics Low 38992889
2023 In mucopolysaccharidosis I cells, GPER1 forms aggregates that disappear when cells are treated with the deficient enzyme (which degrades glycosaminoglycans), suggesting GPER1 aggregation is caused by interaction with accumulated GAGs rather than altered protein expression. Immunofluorescence for GPER1 aggregates, enzyme replacement treatment, transcriptomic analysis, GPER1 gene/protein expression comparison between aggregate-positive and negative conditions European journal of cell biology Low 35537249
2023 GPER1 activation in macrophages inhibits M1 and M2 macrophage polarization via downregulation of MAPK pathways, reducing renal fibrosis in UUO mice; Gper1 deletion in male UUO mice accelerated fibrosis and increased inflammation. GPER1 agonist G-1 in OVX/male UUO mice, Gper1 knockout mice, RNA-sequencing, immunoblotting for MAPK, macrophage co-culture with tubular epithelial cells and fibroblasts Cell death & disease Medium 38086848
2023 GPER1 activation upregulates the miR-29b oncosuppressor network and blunts an established miR-29b-Sp1 feedback loop in multiple myeloma cells, contributing to anti-tumor activity. GPER1 agonist G-1 in MM cells, miR-29b expression analysis, Sp1 pathway analysis, apoptosis assays, in vivo xenograft models Cells Low 37759449
2023 In the placenta, E2 enhances melatonin synthetase AANAT expression and melatonin production in primary human trophoblast cells through the GPER1-PKA-CREB signaling pathway. Primary human trophoblast cells, GPER1 pharmacological agonism, PKA and CREB pathway analysis, AANAT expression and melatonin production assays Journal of pineal research Low 37746893
2022 Bisphenol S (BPS)-induced upregulation of Agrp in hypothalamic neurons is prevented by GPER1 inhibitor G15, establishing that BPS acts through GPER1 to induce Agrp expression independently of Atf3 and Klf4 upregulation. GPER1 inhibitor G15 in immortalized murine hypothalamic cell lines (mHypoE-41, mHypoA-59), Agrp mRNA measurement, transcription factor expression profiling Molecular and cellular endocrinology Low 35569583
2019 GPER1 agonist G-1 activates GPER1/cAMP-dependent Erk/MAPK cascade to upregulate Runx2 osteogenic transcription factor in osteoblasts; G15 (GPER1 antagonist) abolishes prunetin-induced increases in cAMP, osteoblast proliferation, and differentiation. Primary rat osteoblast cultures, HEK293T cells, selective GPER1 agonist G-1, antagonist G15, cAMP measurement, ERK/MAPK inhibition, Runx2 expression analysis, in vivo drill-hole injury rat model The Journal of nutritional biochemistry Low 26345541

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 295 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 150 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 76 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
2014 Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis. PloS one 55 24736568
2014 GPER1 (GPR30) knockout mice display reduced anxiety and altered stress response in a sex and paradigm dependent manner. Hormones and behavior 55 25236887
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
2021 GPER1 is required to protect fetal health from maternal inflammation. Science (New York, N.Y.) 53 33446553
2018 Attenuation of Microbiotal Dysbiosis and Hypertension in a CRISPR/Cas9 Gene Ablation Rat Model of GPER1. Hypertension (Dallas, Tex. : 1979) 51 30354811
2012 Implication of GPER1 in neuroprotection in a mouse model of Parkinson's disease. Neurobiology of aging 49 22749492
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 48 26345541
2012 GPER1/GPR30 activation improves neuronal survival following global cerebral ischemia induced by cardiac arrest in mice. Translational stroke research 48 23483801
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
2011 Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells. Frontiers in bioscience (Landmark edition) 33 21196169
2013 GPCR-mediated rapid, non-genomic actions of steroids: comparisons between DmDopEcR and GPER1 (GPR30). General and comparative endocrinology 32 24188886
2016 Characterisation of Signalling by the Endogenous GPER1 (GPR30) Receptor in an Embryonic Mouse Hippocampal Cell Line (mHippoE-18). PloS one 31 26998610
2019 A Novel Mechanism of S-equol Action in Neurons and Astrocytes: The Possible Involvement of GPR30/GPER1. International journal of molecular sciences 30 31635400
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
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
2013 Vasoconstriction induced by G1, a G-protein-coupled oestrogen receptor1 (GPER-1) agonist, in the isolated perfused rat kidney. European journal of pharmacology 26 23376418
2020 G Protein-Coupled Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive Diseases. Frontiers in endocrinology 25 33281743
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
2015 17β-estradiol inhibits spreading of metastatic cells from granulosa cell tumors through a non-genomic mechanism involving GPER1. Carcinogenesis 25 25823895
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
2019 The neuroprotective effects of novel estrogen receptor GPER1 in mouse retinal ganglion cell degeneration. Experimental eye research 23 31586450
2016 Serum levels of G protein-coupled estrogen receptor 1 (GPER1) in drug-naive patients with generalized anxiety disorder. Psychiatry research 23 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 23 24718680
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 The protective role of G protein-coupled estrogen receptor 1 (GPER-1) on methotrexate-induced nephrotoxicity in human renal epithelium cells. Renal failure 22 26981789
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
2015 Oxidative/antioxidative enzyme-mediated antiproliferative and proapoptotic effects of the GPER1 agonist G-1 on lung cancer cells. Oncology letters 21 26722308
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
2021 Saikosaponin-d alleviates hepatic fibrosis through regulating GPER1/autophagy signaling. Molecular biology reports 20 34714484
2015 Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats. Hormones and behavior 20 26093261
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
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 18 31082617
2020 The GPER1/SPOP axis mediates ubiquitination-dependent degradation of ERα to inhibit the growth of breast cancer induced by oestrogen. Cancer letters 17 33069770
2020 Does GPER1 Play a Role in Sexual Dimorphism? Frontiers in endocrinology 17 33193108
2019 Targeting GPER1 to suppress autophagy as a male-specific therapeutic strategy for iron-induced striatal injury. Scientific reports 17 31040364
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 novel estrogen receptor GPER1 decreases epilepsy severity and susceptivity in the hippocampus after status epilepticus. Neuroscience letters 16 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 16 31698960
2018 Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats. Hormones and behavior 16 29807036
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
2024 Activation of GPER-1 Attenuates Traumatic Brain Injury-Induced Neurological Impairments in Mice. Molecular neurobiology 13 38217667
2023 Knockdown of G Protein-coupled Estrogen Receptor 1 (GPER1) Enhances Tumor-supportive Properties in Cervical Carcinoma Cells. Cancer genomics & proteomics 13 37093686
2023 Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta. Journal of pineal research 13 37746893
2023 Activation of GPER1 in macrophages ameliorates UUO-induced renal fibrosis. Cell death & disease 13 38086848
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
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 Selenium restored mitophagic flux to alleviate cadmium-induced hepatotoxicity by inhibiting excessive GPER1-mediated mitophagy activation. Journal of hazardous materials 10 38880044
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
2023 GPER1 deficiency causes sex-specific dysregulation of hippocampal plasticity and cognitive function. The Journal of endocrinology 10 37399525
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
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 Multiplex G Protein-Coupled Receptor Screen Reveals Reliably Acting Agonists and a Gq-Phospholipase C Coupling Mode of GPR30/GPER1. Molecular pharmacology 9 36400433
2021 G Protein-Coupled Estrogen Receptor 1 (GPER1) Mediates Aldosterone-Induced Endothelial Inflammation in a Mineralocorticoid Receptor-Independent Manner. International journal of endocrinology 9 34239558
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

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