Affinage

Showing NR3C1 — GR is a alias.

NR3C1

Glucocorticoid receptor · UniProt P04150

Length
777 aa
Mass
85.7 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR3C1 encodes the glucocorticoid receptor (GR), a ligand-activated transcription factor that translates corticosteroid signals into broad transcriptional programs governing inflammation, metabolism, and tissue-specific physiology (PMID:21750107, PMID:38533639). Before activation, GR is held in a chaperone cycle: an Hsp90-Hsp70-Hop loading complex recognizes a partially unfolded GR through an extended pocket and poises Hsp90 for ATP hydrolysis, inactivating the receptor, after which an Hsp90-p23 maturation complex threads the ligand-binding domain through the Hsp90 lumen and restores a folded, ligand-bound conformation stabilized by a p23 C-terminal helix (PMID:34937942, PMID:34937936). Once nuclear, GR regulates genes both by direct binding to glucocorticoid response elements and by tethering to partner factors; in zebrafish, tethering rather than direct DNA binding drives Stat3 target induction, and it represses target promoters such as ERβ via GREs (PMID:35269817, PMID:35643536). GR cross-talk reshapes the genome: coactivation with RELA/NF-κB redirects both factors to novel binding sites enriched near mutually antagonized genes (PMID:21750107), GR recruits the demethylase KDM1A to remove preprogrammed H3K4me2 at its binding sites to promote chromatin occupancy (PMID:31216473), it forms a stable, ATP-dependent GR-HMGB1-chromatin complex reflecting kinetic cooperativity (PMID:15808513), and it partners with STAT5A in adipocytes and Myod1 at muscle enhancers in a tissue-specific manner (PMID:17372307, PMID:33836079). These activities drive distinct physiological outputs—diurnal cardiac ion-channel rhythms and arrhythmia susceptibility (Scn5a, Kcnh2, Gja1) (PMID:38533639), adipose lipolysis through an intronic GRE in Atgl (PMID:30649271), muscle mass control (PMID:33836079), and β-cell autophagy via an NR3C1-FTO-m6A-Atg gene axis (PMID:37039556). Loss-of-function NR3C1 mutations identified in Cushing-disease corticotroph tumors impair DEX-induced nuclear translocation and attenuate suppression of POMC transcription (PMID:34427636).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 Medium

    Established that GR transcriptional competence persists across the cell cycle and that apparent G2/M resistance was a synchronization-drug artifact, while regional aging studies showed chaperone-dependent GR nuclear trafficking can be selectively impaired.

    Evidence MMTV reporter assays with cell synchronization and flow cytometry; nuclear/cytosolic fractionation, EMSA, and chaperone measurement in aged rat hippocampus

    PMID:11897693 PMID:12040020

    Open questions at the time
    • Does not identify which chaperones limit translocation with age
    • Does not link cell-cycle competence to specific target-gene programs
  2. 2005 High

    Resolved how GR engages chromatin in living cells, showing GR-HMGB1 association is chromatin-restricted and mutually mobility-limiting, defining kinetic cooperativity as a mechanism of transcription-factor chromatin binding.

    Evidence FRAP and fluorescence correlation spectroscopy in living cells

    PMID:15808513

    Open questions at the time
    • Does not map which GR target loci require HMGB1
    • ATP-consuming disassembly process not molecularly defined
  3. 2011 High

    Defined how GR cross-talk and GR gene regulation are achieved, showing NF-κB coactivation redirects both factors to novel mutually-antagonistic sites, and that alternative first exons impose multilayered control of GR expression.

    Evidence Genome-wide GR/p65 ChIP-seq with expression profiling; promoter/luciferase, mRNA stability and translation-efficiency assays

    PMID:21527501 PMID:21750107

    Open questions at the time
    • Mechanism that recruits both factors to new sites unresolved
    • Promoter-specific physiological consequences of isoform usage not established
  4. 2009 Medium

    Showed that the GRβ isoform has intrinsic, GRα-independent transcriptional activity over a largely distinct gene set, distinguishing isoform-specific programs.

    Evidence Stable EGFP-GRβ HeLa lines with microarray profiling and immunofluorescence

    PMID:19248771

    Open questions at the time
    • Single cell-system; no in vitro reconstitution
    • GRβ DNA-binding/tethering mechanism not defined
  5. 2007 Medium

    Identified STAT5A as a phosphorylation-dependent, tissue-specific nuclear partner of GR in adipocytes, expanding the GR tethering repertoire.

    Evidence Subcellular fractionation, co-immunoprecipitation and Western blot in 3T3-L1/3T3-F442A adipocytes

    PMID:17372307

    Open questions at the time
    • Co-IP without reciprocal or genome-wide validation
    • Target genes of the STAT5A/GR complex not defined
  6. 2008 Medium

    Demonstrated a non-canonical GR activation route in which RXFP1-independent relaxin signaling drives Ser211 phosphorylation and GR-dependent anti-inflammatory output.

    Evidence Receptor-inactive modified relaxin, cytokine assays with GR antagonists, phospho-Ser211 immunostaining and AP-1 reporter in HeLa/endothelial cells

    PMID:19101597

    Open questions at the time
    • Direct relaxin-GR engagement not shown
    • Upstream kinase mediating Ser211 phosphorylation unidentified
  7. 2016 Medium

    Established GR as a haploinsufficient tumor suppressor in BPDCN, linking reduced GR dosage to corticoresistance and loss of EZH2 function.

    Evidence Molecular cytogenetics, targeted deep sequencing, and gene-expression profiling of BPDCN samples

    PMID:27060168

    Open questions at the time
    • Mechanistic link from GR loss to EZH2 dysfunction not resolved
    • Causality of haploinsufficiency not tested by rescue
  8. 2019 High

    Showed how GR shapes its own chromatin access and defined a metabolic target program, identifying KDM1A as an integral nuclear-complex component that erases H3K4me2 to enable GR binding, and an intronic Atgl GRE driving adipose lipolysis.

    Evidence Biochemical complex purification, cell-free demethylation assay and ChIP-seq; adipocyte-specific GR knockout mice with RNA-seq and GRE mapping

    PMID:30649271 PMID:31216473

    Open questions at the time
    • How GR licenses KDM1A specificity at select sites unclear
    • Whether KDM1A recruitment generalizes across GR targets not established
  9. 2021 High

    Resolved the molecular basis of GR chaperone-dependent maturation, capturing the Hsp90-Hsp70-Hop loading complex that inactivates partially unfolded GR and the Hsp90-p23 maturation complex that restores ligand-bound folded GR.

    Evidence Cryo-EM structures of GR loading and maturation complexes with functional validation

    PMID:34937936 PMID:34937942

    Open questions at the time
    • Kinetics of in-cell cycling between complexes not resolved
    • How client-specific folding selectivity is encoded not fully defined
  10. 2021 High

    Extended GR's tissue-specific genomic logic, showing GR co-occupies muscle enhancers with Myod1 and negatively controls muscle mass via Nrf1/Ctcf-anchored enhancer-promoter loops.

    Evidence ChIP-seq, ATAC-seq, 4C/HiC, GR knockout mice with strength/mass measurements

    PMID:33836079

    Open questions at the time
    • Direct GR control of loop architecture versus correlation not separated
    • Anabolic target genes mediating mass loss not fully enumerated
  11. 2021 Medium

    Defined disease-causing GR mutations in Cushing-disease corticotroph tumors that impair nuclear translocation and POMC suppression while increasing proliferation and ACTH output.

    Evidence Tumor sequencing with functional mutagenesis, translocation imaging, proliferation and ACTH assays in AtT-20 cells

    PMID:34427636

    Open questions at the time
    • Structural basis of each mutation's defect not resolved
    • Single corticotroph cell line tested
  12. 2022 Medium

    Genetically dissected GR action mechanisms in vivo, showing tethering (not direct DNA binding) drives Stat3 target induction and that MR cooperates with GR for correct GC-target transcription, and that GR can directly repress the ERβ/TPH2 serotonin pathway.

    Evidence Zebrafish knockout and DNA-binding-mutant lines with RNA-seq; GRE reporter assays and in vivo rescue in stressed/Ahi1-knockout mice

    PMID:35269817 PMID:35643536

    Open questions at the time
    • Tethering partners beyond Stat3 not enumerated
    • Mechanism of GR/MR cooperativity at shared targets undefined
  13. 2023 Medium

    Identified an NR3C1-FTO-m6A axis whereby GR activation upregulates FTO to demethylate core autophagy gene mRNAs, causing hyperactive autophagy and defective insulin secretion in β-cells.

    Evidence RNA-seq, m6A MeRIP-seq, adenoviral overexpression, FTO inhibitor and β-cell-specific NR3C1 overexpression mice with glucose tolerance testing

    PMID:37039556

    Open questions at the time
    • Whether FTO is a direct GR transcriptional target not shown
    • Causal step linking autophagy to secretory failure not isolated
  14. 2024 High

    Established cardiac GR as the driver of diurnal ion-channel rhythms and arrhythmia risk, and revealed GR super-enhancer condensate formation as a transcriptional mechanism in cancer.

    Evidence ATAC-seq, cardiomyocyte-specific GR knockout, electrophysiology and pharmacology; FRAP, ChIP-seq and CUT&Tag with patient-derived models

    PMID:38533639 PMID:39731339

    Open questions at the time
    • Whether condensate formation generalizes beyond gastric cancer untested
    • Direct GR binding at all rhythmic ion-channel loci not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GR integrates ligand-cycling, chaperone state, post-translational modifications, and partner availability to select tissue-specific direct-binding versus tethering programs remains unresolved.
  • No unified model connecting chaperone-cycle output to genomic program choice
  • PTM-to-target-gene mapping incomplete
  • Determinants of direct-GRE versus tethered mode not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
HMGB1HOPHSP70HSP90KDM1AP23RELASTAT5A
Complex memberships
GR-HMGB1-chromatin complexGR-KDM1A nuclear complexHsp90-Hsp70-Hop GR loading complexHsp90-p23 GR maturation complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Cryo-EM structure of the GR-loading complex (Hsp90-Hsp70-Hop-GR) reveals that GR is partially unfolded and recognized through an extended binding pocket composed of Hsp90, Hsp70, and Hop; two Hsp70 molecules are present—one delivers GR and one scaffolds Hop; Hop interacts with all components and poises Hsp90 for ATP hydrolysis, establishing the molecular mechanism of GR loading and inactivation. Cryo-electron microscopy structure determination Nature High 34937942
2021 Cryo-EM structure of the GR-maturation complex (GR-Hsp90-p23) shows that the GR ligand-binding domain is restored to a folded, ligand-bound conformation while threaded through the Hsp90 lumen; p23 directly stabilizes native GR via a C-terminal helix, enhancing ligand binding, revealing that Hsp90 can directly dictate client-specific folding outcomes. Cryo-electron microscopy structure determination Nature High 34937936
2005 In living cells, GR and HMGB1 interact only within chromatin (not in the nucleoplasm) and mutually decrease each other's mobility, forming a potentially stable GR-HMGB1-chromatin complex whose disassembly requires active, ATP-consuming processes; this demonstrates kinetic cooperativity between transcription factors in chromatin binding. FRAP (fluorescence recovery after photobleaching) in living cells, fluorescence correlation spectroscopy Molecular cell High 15808513
2011 Coactivation of GR and RELA (p65/NF-κB) results in their mutual association with novel genomic binding sites not occupied by either factor alone; these novel sites predominantly cluster with target genes antagonized by the opposing factor, demonstrating that GR-NF-κB crosstalk alters the repertoire of binding sites and regulated genes in a mutually dependent manner. Genome-wide ChIP-seq for GR and p65 binding sites combined with gene expression profiling Genome research High 21750107
2009 GRβ isoform has intrinsic, GRα-independent transcriptional activity on endogenous genes, regulating a large and mostly distinct set of genes compared with GRα; in HCT116 cells, GRβ nuclear translocation and activation by RU486 (previously reported) was not observed. Stable EGFP-GRβ expression in HeLa cells, microarray gene expression analysis, immunofluorescence Biochemical and biophysical research communications Medium 19248771
2019 Biochemical purification of the nuclear GR complex identified KDM1A (LSD1) as an integral component; in cell-free assays, GR modulates KDM1A-catalyzed H3K4 progressive demethylation by limiting loss of H3K4me1; in cells, KDM1A removes preprogrammed H3K4me2 at GR binding sites, promoting GR chromatin binding and glucocorticoid-induced gene transcription. Biochemical purification of GR nuclear complex, cell-free histone demethylation assay, ChIP-seq, KDM1A inhibition Cell reports High 31216473
2002 GR is transcriptionally functional throughout the entire cell cycle including G2; GR responsiveness is repressed in mitosis due to chromatin condensation rather than cell cycle-dependent GR phosphorylation; the previously reported G2/M resistance was an artifact of the synchronization drug Hoechst 33342, which independently interferes with GR-dependent transcription. Cell synchronization, stable and transient MMTV-GFP reporter assays, flow cytometry in asynchronous populations Molecular endocrinology Medium 12040020
2007 STAT5A (but not STAT5B) forms a complex with GR in adipocytes; the STAT5A associated with GR in the nucleus is tyrosine-phosphorylated; formation of nuclear STAT5A/GR complexes is regulated in both cytosol and nucleus at distinct times during adipogenesis and in mature adipocytes. Subcellular fractionation, co-immunoprecipitation, Western blotting in 3T3-L1 and 3T3-F442A adipocytes Obesity Medium 17372307
2011 Multiple 5'-untranslated first exons of the GR gene drive alternative promoters that are differentially regulated by growth factor and depolarization-induced signaling; these alternative first exon transcripts differentially control RNA stability and translation efficiency, indicating multilayered transcriptional and posttranscriptional control of GR expression. Promoter characterization, luciferase reporter assays, mRNA stability assays, translation efficiency measurement in mouse tissues Molecular endocrinology Medium 21527501
2021 In skeletal muscle, GR and Myod1 co-occupy numerous muscle-specific enhancers; GR negatively controls muscle mass and strength by down-regulating anabolic pathways; enhancer-promoter communication occurs via CpG-bound transcription factor Nrf1 and Ctcf-anchored chromatin loops in a myofiber-specific manner. ChIP-seq, ATAC-seq, 3D chromatin capture (4C-seq/HiC), GR knockout mice, functional strength and mass measurements Nucleic acids research High 33836079
2002 Nuclear GR protein levels and DNA binding are decreased in aged rat hippocampus; chaperone proteins responsible for GR nuclear translocation are also decreased; intracellular trafficking of GR is specifically impaired in hippocampus with aging but not in hypothalamus, indicating regional specificity. Nuclear/cytosolic fractionation, Western blotting, electrophoretic mobility shift assay (EMSA) for DNA binding, immunostaining Endocrinology Medium 11897693
2017 Zebrafish nr3c1 null mutants generated by CRISPR/Cas9 are viable but show HPI axis dysregulation (elevated cortisol, overactivated crh and pomca), unresponsiveness to mechanical stressors, and abolished inflammatory and anti-inflammatory cytokine responses after intestinal damage, demonstrating GR's dual pro- and anti-inflammatory role in vivo. CRISPR/Cas9 knockout, cortisol measurement, qPCR, dextran sodium sulfate intestinal damage model Scientific reports Medium 28663543
2022 In zebrafish, GR tethering activity (not direct DNA binding) is the primary mechanism for glucocorticoid-induced Stat3 target gene expression; Stat3 target genes are induced by GC in wild-type and in a DNA-binding mutant gr line, but not in gr knockouts. Additionally, mineralocorticoid receptor (MR/nr3c2) is required for correct transcription of several GC-target genes, revealing interplay between GR and MR in GC-dependent transcription. Zebrafish mutant lines (knockout and DNA-binding point mutation), RNA-seq, glucocorticoid treatment International journal of molecular sciences Medium 35269817
2008 Human relaxin-2 activates GR in a manner independent of the membrane receptor RXFP1: RXFP1-inactive modified relaxin retained ability to inhibit TNF-α and IL-6 secretion via GR (blocked by RU-486 and D-06 antagonists), induced Ser211 phosphorylation of GR (a biomarker of agonist-related activation), and caused accumulation of phospho-GR in cytoplasm and nucleus. Modified relaxin (RXFP1-inactive), cytokine secretion assay with GR antagonists, Ser211-phospho-GR immunostaining in HeLa and endothelial cells, AP-1-luciferase assay Regulatory peptides Medium 19101597
2023 NR3C1 activation in pancreatic β-cells under glucolipotoxic conditions upregulates the RNA demethylase FTO, which reduces m6A modifications on mRNAs of four core autophagy genes (Atg12, Atg5, Atg16l2, Atg9a), leading to hyperactive autophagy and defective insulin secretion; FTO inhibition prevented NR3C1-driven excessive autophagy. RNA-seq, m6A MeRIP-seq, adenoviral NR3C1 overexpression, FTO inhibitor (Dac51), β-cell-specific NR3C1 overexpression mice, glucose tolerance testing Autophagy Medium 37039556
2024 Cardiac GR mediates a diurnal rhythm in ventricular arrhythmia susceptibility: GR motifs are enriched in open chromatin at ZT12 (peak corticosteroid time) in ventricular myocytes; GR transcriptionally controls ion channel genes (Scn5a, Kcnh2, Gja1); both pharmacological GR blockade and cardiomyocyte-specific GR knockout abolished ion channel expression rhythms and eliminated ZT12 susceptibility to pacing-induced ventricular arrhythmia. ATAC-seq in ventricular myocyte nuclei, cardiomyocyte-specific GR knockout, electrophysiology, in silico biophysical modeling, pharmacological GR blockade Circulation research High 38533639
2021 NR3C1 transcriptionally regulates ferroptosis-related genes HSPB1 and NCOA4 in glioblastoma cells; ginsenoside Rg5 directly targets NR3C1 and alters HSPB1 and NCOA4 expression to activate ferroptosis and inhibit glioma stem cell properties. RNA sequencing, transcription factor database intersection analysis, luciferase reporter assay, ChIP (implied by transcriptional regulation claim), intracranial xenograft assay Phytomedicine Low 38640858
2021 Three NR3C1 mutations found in Cushing disease corticotroph tumors (p.R469X, p.D590G, p.Y693D) cause decreased DEX-induced GR nuclear translocation, increased cell proliferation, and attenuated suppression of POMC transcription; the p.R469X truncation also increases ACTH secretion compared to wild-type GR in corticotroph cells. Next-generation sequencing of patient tumors, Western blot, immunofluorescence for nuclear translocation, transfection in AtT-20 corticotroph cells, ACTH secretion assay Endocrinology Medium 34427636
2022 GR acts as a transcription factor that binds to glucocorticoid response elements in the ERβ promoter, inhibiting ERβ transcription; this GR-mediated repression of the ERβ/TPH2 pathway reduces serotonin production in male stressed and Ahi1 knockout mice, contributing to depression-like behavior; Ahi1 regulates this pathway by controlling GR nuclear translocation upon stress. Dual-luciferase reporter assay for GR binding to ERβ promoter GREs, Western blot, immunofluorescence, gene knockdown, rescue assay Cell communication and signaling Medium 35643536
2021 FKBP4 regulates NRF2 protein levels (not mRNA) through modulating nuclear translocation of NR3C1/GR in breast cancer cells; naringenin suppresses autophagy and proliferation through the FKBP4/NR3C1/NRF2 signaling axis. siRNA knockdown, Western blot, nuclear translocation assay, in vitro and in vivo tumor models Frontiers in immunology Low 35087512
2021 miR-19b directly targets NR3C1 (confirmed by dual luciferase reporter assay); miR-19b inhibition or NR3C1 overexpression inhibited colon cancer cell proliferation, induced G1/S cell cycle blockade, apoptosis, and chemosensitivity to oxaliplatin via the PI3K/AKT/mTOR pathway. Dual luciferase reporter assay, Western blot, flow cytometry, MTT assay, in vivo xenograft Clinical Medicine Insights. Oncology Medium 34017210
2016 Haploinsufficiency for NR3C1 in BPDCN results in lowered GR expression; functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion, establishing GR as a haploinsufficient tumor suppressor in this leukemia subset. Molecular cloning, FISH/molecular cytogenetics, targeted deep sequencing, functional assays, gene expression profiling Blood Medium 27060168
2019 In adipocyte-specific GR knockout mice under chronic corticosterone treatment, GR drives lipolysis through Atgl via a novel intronic glucocorticoid-responsive element; loss of adipocyte GR results in healthy adipose expansion with diminished ectopic lipid deposition and improved insulin sensitivity, revealing GR-mediated inhibition of healthy adipose expansion in Cushing syndrome. Adipocyte-specific GR knockout mice, RNA-seq, GRE identification in Atgl intron, clinical sample analysis Endocrinology Medium 30649271
2024 SE-driven NR3C1 forms phase-separated condensates (demonstrated by FRAP) and, together with Mediator, promotes SE-related gene transcription via phase separation in gastric cancer; NR3C1 co-occupies super-enhancers (by CUT&Tag) to drive 5-FU resistance-related gene expression. ChIP-seq, CUT&Tag sequencing, FRAP for phase separation, siRNA knockdown, patient-derived organoids, patient-derived xenografts Advanced science Medium 39731339

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience and biobehavioral reviews 259 26073068
2011 Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes. Genome research 175 21750107
2021 Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism. Nature 169 34937942
2013 Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. The international journal of neuropsychopharmacology 168 23449091
2020 C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy. Science translational medicine 162 32878979
2020 Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway. Circulation research 156 33334122
2005 The Y deletion gr/gr and susceptibility to testicular germ cell tumor. American journal of human genetics 151 16380914
2014 Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study. Translational psychiatry 134 24713862
2009 Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity. Biochemical and biophysical research communications 133 19248771
2003 Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. Human mutation 123 12754700
2021 Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism. Nature 120 34937936
2005 GR and HMGB1 interact only within chromatin and influence each other's residence time. Molecular cell 101 15808513
2012 Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and infant neurobehavior. Developmental psychobiology 96 22714792
2005 The Y chromosome gr/gr subdeletion is associated with male infertility. Molecular human reproduction 91 16123079
2018 Glucocorticoid receptor gene (NR3C1) DNA methylation in association with trauma, psychopathology, transcript expression, or genotypic variation: A systematic review. Neuroscience and biobehavioral reviews 79 30176278
2015 Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer. Breast cancer research and treatment 78 25762479
2004 High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Human reproduction (Oxford, England) 78 15513974
2002 Decrements in nuclear glucocorticoid receptor (GR) protein levels and DNA binding in aged rat hippocampus. Endocrinology 76 11897693
2010 What about gr/gr deletions and male infertility? Systematic review and meta-analysis. Human reproduction update 68 20959348
2018 Discovery of a Glucocorticoid Receptor (GR) Activity Signature Using Selective GR Antagonism in ER-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 62 29636357
2016 Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms. Blood 59 27060168
2009 Y chromosome gr/gr deletions are a risk factor for low semen quality. Human reproduction (Oxford, England) 59 19602516
2017 nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor. Scientific reports 58 28663543
2016 Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacology & therapeutics 58 27288728
2020 GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection. mBio 57 32820005
2008 Understanding the multiple functions of Gr-1(+) cell subpopulations during microbial infection. Immunologic research 57 18193362
2018 NR3C1 hypermethylation in depressed and bullied adolescents. Translational psychiatry 56 29921868
2014 Glucocorticoid regulation of lung development: lessons learned from conditional GR knockout mice. Molecular endocrinology (Baltimore, Md.) 56 25535891
2004 Getting a GR(i)P on oligodendrocyte development. Developmental biology 56 14697351
2016 Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses. Scientific reports 54 26876364
2023 NR3C1/Glucocorticoid receptor activation promotes pancreatic β-cell autophagy overload in response to glucolipotoxicity. Autophagy 48 37039556
2022 Crosstalk between p38 MAPK and GR Signaling. International journal of molecular sciences 48 35328742
2013 Nuclear receptors in inflammation control: repression by GR and beyond. Molecular and cellular endocrinology 48 23623868
2019 Aberrant Epigenomic Modulation of Glucocorticoid Receptor Gene (NR3C1) in Early Life Stress and Major Depressive Disorder Correlation: Systematic Review and Quantitative Evidence Synthesis. International journal of environmental research and public health 45 31689998
2022 Naringenin Regulates FKBP4/NR3C1/NRF2 Axis in Autophagy and Proliferation of Breast Cancer and Differentiation and Maturation of Dendritic Cell. Frontiers in immunology 42 35087512
2020 Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism. Frontiers in endocrinology 40 33133019
2020 DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. Psychological trauma : theory, research, practice and policy 39 32212777
2016 FKBP5 mRNA Expression Is a Biomarker for GR Antagonism. The Journal of clinical endocrinology and metabolism 39 27459525
2021 Discovery of Novel GR Ligands toward Druggable GR Antagonist Conformations Identified by MD Simulations and Markov State Model Analysis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 36 34825505
2006 Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity. BMC medical genetics 35 16725041
2021 Glucocorticoid receptor gene (NR3C1) methylation during the first thousand days: Environmental exposures and developmental outcomes. Neuroscience and biobehavioral reviews 34 33689802
2011 Hippocampal GR expression is increased in elderly depressed females. Neuropharmacology 34 21945289
2010 Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients. European journal of human genetics : EJHG 34 20823911
2022 The long winding road to the safer glucocorticoid receptor (GR) targeting therapies. Oncotarget 33 35198100
2015 Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study. Journal of affective disorders 33 25889020
2015 Glucocorticoid receptor gene (NR3C1) promoter is hypermethylated in Thai females with major depressive disorder. Genetics and molecular research : GMR 33 26782558
2019 GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life. Frontiers in immunology 32 31379877
2016 HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome. Diabetes/metabolism research and reviews 32 27507764
2002 Activity of the GR in G2 and mitosis. Molecular endocrinology (Baltimore, Md.) 31 12040020
2019 GR and LSD1/KDM1A-Targeted Gene Activation Requires Selective H3K4me2 Demethylation at Enhancers. Cell reports 30 31216473
2017 Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function. Andrology 29 28992366
2015 Cardiac GR and MR: From Development to Pathology. Trends in endocrinology and metabolism: TEM 29 26586027
2011 Differential regulation and function of 5'-untranslated GR-exon 1 transcripts. Molecular endocrinology (Baltimore, Md.) 29 21527501
2022 Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors. Cell communication and signaling : CCS 28 35643536
2021 Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation. Scientific reports 28 33762648
2021 Myod1 and GR coordinate myofiber-specific transcriptional enhancers. Nucleic acids research 27 33836079
1991 A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp. Biochemical genetics 27 1679325
2020 DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia. Journal of molecular neuroscience : MN 26 32281042
2017 Hippocampal GR- and CB1-mediated mGluR5 differentially produces susceptibility and resilience to acute and chronic mild stress in rats. Neuroscience 26 28629846
2024 Ginsenoside Rg5 inhibits glioblastoma by activating ferroptosis via NR3C1/HSPB1/NCOA4. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 38640858
2020 GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy. BMC cancer 25 32106831
2019 Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association. Journal of psychiatric research 25 31731185
2016 Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells. Molecular and cellular biochemistry 24 27632388
2016 Medical morbidities and DNA methylation of NR3C1 in preterm infants. Pediatric research 23 27653086
2008 RXFP1-inactive relaxin activates human glucocorticoid receptor: further investigations into the relaxin-GR pathway. Regulatory peptides 23 19101597
2023 Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions. Cell reports 22 37471224
2015 The NR3C1 Glucocorticoid Receptor Gene Polymorphisms May Modulate the TGF-beta mRNA Expression in Asthma Patients. Inflammation 22 25649164
2021 Effect of 3 NR3C1 Mutations in the Pathogenesis of Pituitary ACTH Adenoma. Endocrinology 21 34427636
2019 DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex. Infant mental health journal 21 31066465
2019 The GR-ANXA1 pathway is a pathological player and a candidate target in epilepsy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 31618599
2018 Glucocorticoid receptor gene variants and lower expression of NR3C1 are associated with cocaine use. Addiction biology 20 29761890
2007 The modulation of STAT5A/GR complexes during fat cell differentiation and in mature adipocytes. Obesity (Silver Spring, Md.) 20 17372307
2021 Role of NR3C1 and SLC6A4 methylation in the HPA axis regulation in burnout. Journal of affective disorders 19 34509065
2021 Perinatal stress and methylation of the NR3C1 gene in newborns: systematic review. Epigenetics 19 34519616
2019 Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age. Frontiers in behavioral neuroscience 18 30804765
2019 DNA Hypomethylation of GR Promoters is Associated with GR Activation and BDNF/AKT/ERK1/2-Induced Hippocampal Neurogenesis in Mice Derived From Folic-Acid-Supplemented Dams. Molecular nutrition & food research 18 30920123
2018 GR-regulating Serine/Threonine Kinases: New Physiologic and Pathologic Implications. Trends in endocrinology and metabolism: TEM 18 29501228
2024 Super-enhancer Activates Master Transcription Factor NR3C1 Expression and Promotes 5-FU Resistance in Gastric Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39731339
2019 NR3C1 gene polymorphisms are associated with high-altitude pulmonary edema in Han Chinese. Journal of physiological anthropology 17 30999951
2018 Engineering Lactobacillus rhamnosus GG and GR-1 to express HIV-inhibiting griffithsin. International journal of antimicrobial agents 17 30040991
2021 Clinical Correlates of the NR3C1 Gene Methylation at Various Stages of Psychosis. The international journal of neuropsychopharmacology 16 33284958
2021 p53 Transactivation Domain Mediates Binding and Phase Separation with Poly-PR/GR. International journal of molecular sciences 16 34768862
2019 Adipocyte GR Inhibits Healthy Adipose Expansion Through Multiple Mechanisms in Cushing Syndrome. Endocrinology 16 30649271
2019 gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study. European journal of human genetics : EJHG 16 31053779
2018 Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms. Endocrinology 16 29762667
2022 Hypothalamic NR3C1 DNA methylation in rats exposed to prenatal stress. Molecular biology reports 15 35661969
2021 NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies. Cells 15 34831409
2013 Transcript variants of the porcine glucocorticoid receptor gene (NR3C1). General and comparative endocrinology 15 23684967
2023 DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression. Journal of affective disorders 13 36933666
2023 Specificity protein 1 (Sp1) and glucocorticoid receptor (GR) stimulate bovine alphaherpesvirus 1 (BoHV-1) replication and cooperatively transactivate the immediate early transcription unit 1 promoter. Journal of virology 13 38084958
2021 The Glucocorticoid Receptor Gene (NR3C1) 9β SNP Is Associated with Posttraumatic Stress Disorder. Healthcare (Basel, Switzerland) 13 33562675
2021 MicroRNA-19b Downregulates NR3C1 and Enhances Oxaliplatin Chemoresistance in Colon Cancer via the PI3K/AKT/mTOR Pathway. Clinical Medicine Insights. Oncology 13 34017210
2020 Dual biomarkers long non-coding RNA GAS5 and its target, NR3C1, contribute to acute myeloid leukemia. Experimental and molecular pathology 13 32032633
2019 Role of NR3C1 and GAS5 genes polymorphisms in multiple sclerosis. The International journal of neuroscience 13 31724909
2016 Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog. Reproduction (Cambridge, England) 13 27530348
2022 Zebrafish Mutant Lines Reveal the Interplay between nr3c1 and nr3c2 in the GC-Dependent Regulation of Gene Transcription. International journal of molecular sciences 12 35269817
2018 Association between NR3C1 rs41423247 polymorphism and depression: A PRISMA-compliant meta-analysis. Medicine 12 30278546
2014 Porcine glucocorticoid receptor (NR3C1) gene: tissue-specificity of transcriptional strength and glucocorticoid responsiveness of alternative promoters. The Journal of steroid biochemistry and molecular biology 12 24503296
2014 Y chromosome gr/gr subdeletion is associated with lower semen quality in young men from the general Japanese population but not in fertile Japanese Men. Biology of reproduction 12 24759788
2024 Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility. Circulation research 11 38533639

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