Affinage

NR3C1

Glucocorticoid receptor · UniProt P04150

Round 2 corrected
Length
777 aa
Mass
85.7 kDa
Annotated
2026-04-29
130 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR3C1 (glucocorticoid receptor, GR) is a ligand-activated nuclear receptor that transduces glucocorticoid signals into diverse transcriptional programs governing inflammation, metabolism, energy balance, and stress-axis programming. Upon glucocorticoid binding, GR is folded and activated through a chaperone cycle involving Hsp90–Hsp70–Hop loading and Hsp90–p23 maturation complexes, then translocates to the nucleus via dynein-dependent transport modulated by FKBP51/52 immunophilins (PMID:34937942, PMID:34937936, PMID:15591061). GR binds DNA as monomers at half-sites or homodimers at palindromic GREs—where the DNA sequence itself allosterically tunes receptor conformation and output—and its anti-inflammatory transrepression of NF-κB requires HDAC2-mediated deacetylation at K494/K495 enabling direct GR–p65 interaction, while transactivation involves coactivators including p300, KDM1A/LSD1-directed H3K4 demethylation, and circadian gating by CRY1/2 (PMID:19372434, PMID:16380507, PMID:31216473, PMID:22170608, PMID:8290595). GR expression is itself epigenetically regulated through NR3C1 promoter methylation at NGFI-A binding sites, providing a molecular mechanism linking early-life adversity to lasting alterations in HPA-axis reactivity (PMID:19234457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1985 High

    Cloning of NR3C1 established the primary structure of the glucocorticoid receptor and identified two splice isoforms (α and β) with intrinsic steroid-binding activity, providing the molecular foundation for all subsequent mechanistic work.

    Evidence cDNA cloning and in vitro translation with radioligand binding

    PMID:2867473

    Open questions at the time
    • No information on three-dimensional structure
    • Functional difference between α and β isoforms not yet characterized
  2. 1991 High

    Crystal structures of the GR DNA-binding domain complexed with DNA revealed zinc-nucleated substructures and a dimerization interface, establishing how GR reads GRE half-site spacing to achieve target specificity.

    Evidence X-ray crystallography of GR DBD–DNA complex

    PMID:1865905

    Open questions at the time
    • Ligand-binding domain structure unresolved
    • Monomer versus dimer binding prevalence in vivo unknown
  3. 1994 High

    Demonstration that GR physically interacts with NF-κB p65 and that each factor antagonizes the other's transcriptional activity established the transrepression paradigm central to glucocorticoid anti-inflammatory action.

    Evidence Reciprocal co-immunoprecipitation, protein crosslinking, and transfection reporter assays

    PMID:7823959 PMID:8290595

    Open questions at the time
    • Mechanism of transrepression (chromatin-based vs. squelching) not yet resolved
    • Whether transrepression operates through the same mechanism at all inflammatory gene loci unknown
  4. 1995 High

    Characterization of GRβ as a ligand-independent dominant-negative inhibitor of GRα established a receptor-intrinsic mechanism for modulating glucocorticoid sensitivity.

    Evidence Radioligand binding, GRE EMSA, and reporter assays comparing α and β isoforms

    PMID:7769088

    Open questions at the time
    • Whether GRβ has autonomous transcriptional activity remained disputed
    • Physiological tissues/conditions where GRβ dominance is functionally relevant were unknown
  5. 1996 High

    Discovery that Stat5 forms a physical complex with GR that binds DNA independently of GREs revealed GR could serve as a co-activator on non-canonical response elements, broadening the receptor's transcriptional repertoire.

    Evidence Co-immunoprecipitation, EMSA, co-transfection reporter assays

    PMID:8878484

    Open questions at the time
    • Isoform specificity (STAT5A vs. STAT5B) of the GR interaction not resolved until later
    • Genomic binding sites of the Stat5–GR complex not identified
  6. 2000 High

    Showing that GR recruits HDAC2 to the p65–CBP complex to suppress histone acetylation at inflammatory promoters provided the first chromatin-level mechanism for GR-mediated transrepression.

    Evidence ChIP, HAT/HDAC activity assays, co-immunoprecipitation at GM-CSF promoter

    PMID:10958685

    Open questions at the time
    • Whether HDAC2 recruitment is universal across all GR-repressed inflammatory genes unknown
    • Post-translational regulation of GR enabling HDAC2 recruitment not yet identified
  7. 2001 High

    Identification of CHIP as a ubiquitin ligase that disrupts Hsp90–GR heterocomplexes and targets GR for proteasomal degradation established protein triage as a regulatory layer controlling GR protein levels.

    Evidence Co-IP, ubiquitylation assays, steroid-binding and reporter assays

    PMID:11146632

    Open questions at the time
    • Whether CHIP-mediated degradation is regulated by specific signals or constitutive not determined
    • Other E3 ligases for GR not explored
  8. 2002 High

    The LBD crystal structure with dexamethasone and TIF2 coactivator peptide defined the ligand pocket, a novel dimer interface, and the charge clamp governing coactivator selectivity, providing a structural basis for selective GR modulator design.

    Evidence X-ray crystallography, site-directed mutagenesis, transcription assays

    PMID:12151000

    Open questions at the time
    • Full-length GR structure including interdomain contacts remained unresolved
    • How the dimer interface operates in the context of chromatin-bound GR unknown
  9. 2002 High

    Conditional GR deletion in the nervous system showed that central GR signaling is required for normal energy balance, growth, and HPA-axis regulation, establishing non-immune physiological roles for GR in the CNS.

    Evidence Conditional Cre-lox knockout mouse with metabolic and neuroendocrine phenotyping

    PMID:12021198

    Open questions at the time
    • Specific neuronal populations mediating each phenotype not identified
    • Downstream transcriptional targets in CNS neurons not mapped
  10. 2005 High

    Multiple studies in this period resolved key regulatory layers: FKBP51/52 control of dynein-mediated GR nuclear translocation, HDAC2-mediated deacetylation of GR K494/K495 as a prerequisite for GR–NF-κB interaction, chromatin-restricted GR–HMGB1 cooperativity, and GR disruption of p65/IRF complexes in TLR-specific transrepression.

    Evidence Domain-swap mutagenesis and dynamitin overexpression (FKBP51/52); site-directed K→A mutagenesis with co-IP and RNAi (HDAC2); live-cell FRAP/FCCS (HMGB1); ChIP with siRNA and expression profiling in macrophages (TLR selectivity)

    PMID:15591061 PMID:15808513 PMID:16143103 PMID:16380507

    Open questions at the time
    • How FKBP51/52 ratio is regulated in different tissues not established
    • Whether HDAC2-dependent deacetylation is the sole switch for GR–NF-κB interaction unknown
    • Genome-wide mapping of HMGB1–GR co-occupied sites not performed
  11. 2005 High

    HDAC6-mediated deacetylation of Hsp90 was shown to be required for Hsp90 chaperone function and consequently for GR ligand binding, nuclear translocation, and transcriptional activity, linking cytoplasmic acetylation signaling to receptor maturation.

    Evidence In vitro deacetylase assay, HDAC6-knockout cells, GR ligand binding and reporter assays

    PMID:15916966

    Open questions at the time
    • Whether HDAC6 regulation of Hsp90 is dynamically modulated under physiological stress unknown
    • Relative contribution of HDAC6 vs. other HDACs to Hsp90 acetylation state not determined
  12. 2009 High

    Structural and functional evidence that single-base-pair differences in GRE sequences allosterically change GR conformation and transcriptional output established DNA as a sequence-specific allosteric ligand of GR, explaining how the same receptor activates different gene programs.

    Evidence X-ray crystallography of GR DBD on variant GREs, biochemical binding assays, cell-based reporter assays

    PMID:19372434

    Open questions at the time
    • Whether DNA allostery propagates to the LBD and coactivator recruitment in full-length GR unknown
    • Number of functionally distinct GRE classes genome-wide not determined
  13. 2009 High

    Linking childhood abuse to increased NR3C1 promoter methylation, reduced hippocampal GR expression, and impaired NGFI-A binding in human postmortem tissue established an epigenetic mechanism for early-life programming of HPA-axis reactivity.

    Evidence Postmortem bisulfite sequencing, patch-methylation reporter assays, NGFI-A EMSA

    PMID:19234457

    Open questions at the time
    • Causal direction (methylation→GR reduction→HPA dysregulation) not fully established in living humans
    • Cell-type specificity of methylation changes within hippocampus unknown
  14. 2010 High

    Discovery that the lncRNA GAS5 mimics a GRE to competitively sequester GR away from chromosomal targets introduced noncoding RNA-mediated decoy regulation as a layer controlling GR transcriptional output and cell survival.

    Evidence RNA–protein binding assay, GR mutagenesis, GRE competition reporter, apoptosis assays

    PMID:20124551

    Open questions at the time
    • In vivo relevance and tissue specificity of GAS5–GR interaction not established
    • Structural basis of GR DBD recognition of RNA vs. DNA GRE not resolved
  15. 2011 High

    CRY1/2 were identified as ligand-dependent GR-interacting partners that globally oppose GR transactivation while modulating the circadian amplitude of glucocorticoid-responsive gene expression, linking the circadian clock to metabolic GR output.

    Evidence Co-IP, genome-wide expression profiling, ChIP at PEPCK1 promoter, CRY-knockout mouse metabolic phenotyping

    PMID:22170608

    Open questions at the time
    • Mechanism by which CRY proteins repress GR transactivation at the structural level unknown
    • Whether CRY modulation applies to GR transrepression of inflammatory genes not tested
  16. 2011 High

    Genome-wide ChIP-seq showed that co-activation of GR and NF-κB p65 generates novel shared binding sites not occupied by either factor alone, redefining transrepression as a genomic redistribution event rather than simple mutual inhibition.

    Evidence ChIP-seq and RNA-seq in cells co-stimulated with dexamethasone and TNFα

    PMID:21750107

    Open questions at the time
    • Whether redistribution requires direct GR–p65 protein interaction at each site unknown
    • Contribution of chromatin accessibility changes vs. cooperative binding not disentangled
  17. 2015 High

    High-resolution ChIP-exo in mouse liver showed that under physiological corticosterone, GR monomers predominate at half-site motifs near lineage-determining factors, while pharmacological glucocorticoids drive dimer assembly at palindromic GREs, resolving the long-debated monomer/dimer question in a physiological context.

    Evidence ChIP-exo in mouse liver and primary macrophages with endogenous vs. pharmacological GC treatment

    PMID:25957148

    Open questions at the time
    • Whether monomer-to-dimer transition occurs at individual loci or reflects population-level redistribution unclear
    • How monomer vs. dimer binding determines transcriptional output at specific genes not resolved
  18. 2016 High

    Identification of three NR3C1 missense mutations (R477S, Y478C, L672P) causing generalized glucocorticoid resistance, with defined molecular defects in DNA binding, nuclear translocation, or ligand binding, linked specific structural domains to clinical disease.

    Evidence Patient genotyping, dexamethasone binding assays, nuclear translocation, ChIP, structural modeling

    PMID:27120390

    Open questions at the time
    • Genotype–phenotype correlation across all known NR3C1 mutations not systematically compiled
    • Whether compensatory GR isoform expression modulates disease severity unknown
  19. 2019 High

    KDM1A/LSD1 was identified as an integral subunit of the nuclear GR complex that progressively demethylates H3K4me2 to H3K4me1 at GR binding sites; GR limits further demethylation, and KDM1A catalytic activity is required for GR chromatin occupancy, establishing an epigenetic prerequisite for GR binding.

    Evidence Biochemical purification, in vitro demethylase assay, ChIP-seq, KDM1A pharmacological inhibition

    PMID:31216473

    Open questions at the time
    • Whether other histone demethylases cooperate with or antagonize KDM1A at GR sites unknown
    • How GR mechanistically limits KDM1A processivity not structurally resolved
  20. 2021 High

    Cryo-EM structures of the GR–Hsp90–Hsp70–Hop loading complex and the GR–Hsp90–p23 maturation complex revealed the complete chaperone cycle at atomic resolution: GR is partially unfolded during loading, then refolded to a ligand-competent state during maturation, resolving decades of biochemical inference.

    Evidence Cryo-electron microscopy with ligand-binding validation

    PMID:34937936 PMID:34937942

    Open questions at the time
    • Whether the chaperone cycle operates identically for other nuclear receptors not demonstrated
    • Dynamics of the loading-to-maturation transition in living cells not captured
  21. 2021 High

    Genome-wide analysis in skeletal muscle revealed GR–Myod1 co-occupancy at enhancers connected to target gene promoters via Ctcf-anchored loops and Nrf1-mediated contacts, demonstrating lineage-specific chromatin architecture as a determinant of GR transcriptional output in muscle.

    Evidence ChIP-seq, 3C/Hi-C, conditional GR knockout with muscle function assays

    PMID:33836079

    Open questions at the time
    • Whether GR uses analogous looping mechanisms in other tissues not tested
    • Structural basis of GR–Myod1 physical interaction not defined
  22. 2023 High

    NR3C1 activation in pancreatic β-cells was shown to upregulate FTO, reducing m6A on autophagy gene mRNAs and driving hyperactive autophagy that impairs insulin secretion, revealing an epitranscriptomic effector arm of GR signaling.

    Evidence RNA-seq, MeRIP-seq, AAV-mediated NR3C1 overexpression mouse model, FTO inhibitor rescue, GSIS assay

    PMID:37039556

    Open questions at the time
    • Whether GR–FTO–m6A axis operates in non-β-cell contexts unknown
    • Direct GR binding to FTO promoter not confirmed by ChIP in this study
  23. 2024 Medium

    NR3C1 was found to form liquid-liquid phase separation condensates at super-enhancers with Mediator, promoting transcription of genes conferring 5-FU resistance in gastric cancer, introducing phase separation as a mechanism for GR-driven oncogenic gene regulation.

    Evidence CUT&Tag, ChIP-seq, FRAP (phase separation), PDO/PDX pharmacological validation

    PMID:39731339

    Open questions at the time
    • Whether GR phase separation occurs under physiological glucocorticoid signaling not tested
    • Structural determinants of GR condensate formation (IDR vs. LBD vs. DBD) not defined
    • Independent replication of GR phase separation at super-enhancers needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the full-length GR structure in the context of chromatin, how monomer vs. dimer binding is regulated at individual loci to produce gene-specific outputs, the structural basis of GR recognition of RNA decoys (GAS5) vs. DNA GREs, and whether GR phase separation is a general mechanism or a context-specific phenomenon.
  • No full-length GR structure on nucleosomal DNA
  • Monomer-to-dimer switching mechanism at individual loci unresolved
  • Structural basis of GR–RNA (GAS5) interaction unknown
  • In vivo relevance of GR liquid-liquid phase separation unconfirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 8 GO:0005694 chromosome 4 GO:0005829 cytosol 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-8953854 Metabolism of RNA 1 R-HSA-9612973 Autophagy 1 R-HSA-9909396 Circadian clock 1
Partners
CRY1FKBP4FKBP5HDAC2HSP90AA1KDM1ARELASTAT5A
Complex memberships
GR–KDM1A chromatin complexGR–NF-κB transrepression complexHsp90–Hsp70–Hop loading complexHsp90–p23 maturation complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 The human glucocorticoid receptor (NR3C1) was cloned and its primary structure determined, predicting two protein isoforms (alpha: 777 aa; beta: 742 aa) differing at their carboxy termini, with a cysteine/lysine/arginine-rich region defining the DNA-binding domain; in vitro synthesized receptor was immunoreactive and possessed intrinsic steroid-binding activity. cDNA cloning, in vitro translation, radioligand binding assay Nature High 2867473
1991 Crystal structures of the glucocorticoid receptor DNA-binding domain (DBD) complexed with DNA revealed a globular fold with two zinc-nucleated substructures; the DBD dimerizes upon DNA binding, placing subunits in adjacent major grooves, and the spacing between half-sites in the target sequence is a critical determinant of binding specificity. X-ray crystallography of GR DBD–DNA complex Nature High 1865905
1994 The GR physically associates with the p65 subunit of NF-κB in intact cells (via protein crosslinking and co-immunoprecipitation) and this interaction mediates mutual transcriptional antagonism: activated GR inhibits NF-κB-driven IL-6 promoter activation, and p65 overexpression inhibits GR-driven MMTV promoter activation. Co-immunoprecipitation, protein crosslinking, transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America High 8290595
1995 Activated GR inhibits NF-κB (p65, p50) by direct protein–protein interaction; the GR zinc-finger (DBD) domain is required; dexamethasone-activated GR reduces nuclear NF-κB DNA binding and transcriptional activation; a transactivation-deficient GR mutant and RU486-treated wild-type GR can each repress p65 activity, indicating transrepression is separable from transactivation. Transfection reporter assays, EMSA, co-immunoprecipitation, site-directed mutagenesis Molecular and cellular biology High 7823959
1995 The human GRβ isoform, generated by alternative splicing of exon 9, does not bind glucocorticoids and is transcriptionally inactive on GRE-driven promoters, but competitively inhibits ligand-activated GRα transcriptional activity in a concentration-dependent manner, likely by competing for GRE binding; GRβ is expressed in multiple human tissues. Radioligand binding assay, GRE EMSA, transfection reporter assay, RT-PCR The Journal of clinical investigation High 7769088
1996 Stat5 physically interacts with the glucocorticoid receptor to form a complex that binds DNA independently of the GRE; this interaction enables GR to act as a transcriptional co-activator enhancing Stat5-dependent gene transcription, while simultaneously the Stat5–GR complex reduces GRE-mediated glucocorticoid responses. Co-immunoprecipitation, EMSA, co-transfection reporter assay Nature High 8878484
2000 Dexamethasone-activated GR recruits histone deacetylase 2 (HDAC2) to the p65-CBP HAT complex, directly inhibiting CBP-associated HAT activity and suppressing IL-1β-stimulated H4K8 and H4K12 acetylation at the GM-CSF promoter; this HDAC2 recruitment is a mechanism by which GR represses inflammatory gene expression beyond simple competition with transcription factors. Chromatin immunoprecipitation, HAT/HDAC activity assays, co-immunoprecipitation Molecular and cellular biology High 10958685
2001 CHIP (carboxyl terminus of Hsc70-interacting protein) incorporates into Hsp90 heterocomplexes, causes release of p23 co-chaperone, abolishes GR steroid-binding activity and transactivation potential, and induces GR ubiquitylation followed by proteasomal degradation, thus functioning as a mediator of protein triage that shifts the chaperone system toward GR degradation. Co-immunoprecipitation, ubiquitylation assay, steroid-binding assay, reporter transactivation assay Nature cell biology High 11146632
2002 GR itself is fully functional throughout the cell cycle in G2; repression of GR-dependent transcription in mitosis is due to chromatin condensation rather than cell-cycle-specific phosphorylation of GR, as demonstrated with multiple stably and transiently transfected promoters and flow cytometric correlation of DEX-induced GFP expression with cell cycle position. Cell synchronization, stable/transient reporter transfection, flow cytometry, live-cell fluorescence Molecular endocrinology (Baltimore, Md.) Medium 12040020
2002 Conditional inactivation of GR selectively in the nervous system of mice causes marked growth retardation, transient increase in body fat during suckling, reduced food intake after weaning, elevated plasma GC and hypothalamic CRH/NPY levels, and disturbed leptin control, demonstrating that central GR signaling is required for normal energy balance regulation. Conditional knockout mouse model (Cre-lox), metabolic phenotyping, hormone measurement, in situ hybridization Endocrinology High 12021198
2002 Crystal structure of the human GR ligand-binding domain (LBD) bound to dexamethasone and a TIF2 coactivator LxxLL motif revealed a novel dimer interface involving an intermolecular β-sheet; this dimer interface is functionally important for GR-mediated transcriptional activation; the structure also defined an additional charge clamp determining coactivator binding selectivity and a distinct ligand-binding pocket explaining hormone selectivity. X-ray crystallography, site-directed mutagenesis, functional transcription assays Cell High 12151000
2004 FKBP51 delays nuclear translocation of GR by reducing its interaction with the motor protein dynein, whereas FKBP52 promotes nuclear translocation by robust dynein association; three features of these immunophilins—Hsp90 interaction, dynein association, and PPIase activity—are each required for efficient GR signaling; swapping the PPIase domains of FKBP51 and FKBP52 reverses their respective effects on GR. Nuclear translocation assay, co-immunoprecipitation, reporter transactivation, domain-swap mutagenesis, dynamitin overexpression The Journal of biological chemistry High 15591061
2005 HDAC6 deacetylates Hsp90; HDAC6 inactivation leads to Hsp90 hyperacetylation, dissociation of the p23 co-chaperone from Hsp90, and loss of chaperone activity; in HDAC6-deficient cells, GR maturation is compromised, resulting in defective GR ligand binding, nuclear translocation, and transcriptional activation. In vitro deacetylase assay, co-immunoprecipitation, ligand binding assay, nuclear translocation assay, reporter assay, HDAC6-knockout cells Molecular cell High 15916966
2005 GR and HMGB1 interact exclusively within chromatin (not in the nucleoplasm), as demonstrated by FRAP and fluorescence cross-correlation in living cells; each factor decreases the other's mobility on chromatin (kinetic cooperativity); disassembly of the GR–HMGB1–chromatin complex requires active, ATP-consuming processes. FRAP, fluorescence cross-correlation spectroscopy (live-cell imaging), chromatin fractionation Molecular cell High 15808513
2005 GR represses TLR4- and TLR9-initiated (MyD88-dependent) inflammatory transcription by disrupting p65/IRF complexes required for those pathogen-specific gene programs, while leaving TLR3-dependent responses unaffected; PPARγ and LXRs use p65/IRF3-independent mechanisms and cooperate with GR to synergistically transrepress distinct subsets of TLR-responsive genes. ChIP, genome-wide expression profiling, siRNA knockdown, co-immunoprecipitation, reporter assays in macrophages Cell High 16143103
2005 GR deacetylation by HDAC2 at K494 and K495 is required for GR to interact with the NF-κB complex and repress NF-κB-mediated inflammatory gene expression; ligand-bound GR becomes acetylated, and HDAC2-mediated deacetylation enables the GR–NF-κB association; loss of HDAC2 (as in COPD) impairs GR–NF-κB interaction without affecting GRE-mediated transactivation. RNA interference, co-immunoprecipitation, site-directed mutagenesis (K494A/K495A), ChIP, reporter assay The Journal of experimental medicine High 16380507
2009 Childhood abuse in humans is associated with decreased GR (NR3C1) mRNA expression in hippocampus, increased cytosine methylation of the NR3C1 1F promoter, and reduced NGFI-A transcription factor binding; patch-methylated NR3C1 promoter constructs mimicking the abused state showed decreased NGFI-A binding and NGFI-A-inducible transcription, demonstrating a functional epigenetic mechanism linking early adversity to altered GR expression. Postmortem brain tissue methylation analysis, patch-methylation reporter assay, NGFI-A EMSA, qRT-PCR Nature neuroscience High 19234457
2009 GR binding sequences (GREs) differing by as little as a single base pair differentially alter GR conformation and transcriptional regulatory activity; DNA acts as a sequence-specific allosteric ligand of GR, structurally tuning the receptor toward specific target gene outputs, as demonstrated by crystallography, biochemical assays, and cell-based transcription assays. X-ray crystallography, biochemical binding assays, cell-based transcriptional reporter assays Science (New York, N.Y.) High 19372434
2009 GRβ isoform has intrinsic, GRα-independent transcriptional activity on a large number of endogenous genes (both activation and repression), distinct from genes regulated by GRα; GRβ does not translocate to the nucleus in response to RU486 in HCT116 cells, contrary to prior reports. Stable EGFP-GRβ expression in HeLa cells, microarray gene expression profiling, nuclear translocation assay Biochemical and biophysical research communications Medium 19248771
2010 The noncoding RNA GAS5 acts as a 'riborepressor' of GR by binding to the GR DNA-binding domain using a sequence that mimics a glucocorticoid response element (decoy GRE); GAS5 thereby competes with chromosomal GREs for GR binding, suppresses GR-mediated induction of anti-apoptotic genes (including cIAP2), and sensitizes cells to apoptosis; GAS5 is upregulated during growth arrest/starvation. RNA-protein binding assay, reporter assay, GR mutational analysis, apoptosis assay, RNA overexpression/knockdown Science signaling High 20124551
2011 Cryptochromes 1 and 2 (CRY1/2) interact with GR in a ligand-dependent manner and globally oppose GR transcriptional activation; cryptochrome deficiency approximately doubles the number of dexamethasone-induced genes and vastly decreases gene repression; CRY1/2 associate with a GRE in the PEPCK1 promoter in a hormone-dependent manner; in vivo, CRY-deficient mice show glucose intolerance and constitutively elevated corticosterone, indicating disinhibited HPA axis and increased hepatic GR transactivation. Co-immunoprecipitation, genome-wide expression profiling, ChIP, knockout mouse metabolic phenotyping Nature High 22170608
2011 Coactivation of GR and NF-κB p65 in cells results in their mutual association with novel, shared genomic binding sites not occupied by either factor alone; these novel sites predominantly cluster with p65 target genes antagonized by GR and vice versa, demonstrating that simultaneous activation of both factors alters the repertoire of regulated genes and binding sites in a mutually dependent manner. ChIP-seq, RNA-seq, genome-wide binding site analysis Genome research High 21750107
2011 Alternative first exons of the mouse/rat/human GR gene are differentially regulated by growth factor and depolarization signals; individual alternative promoter transcripts differentially control RNA stability and translation efficiency, providing multilayered transcriptional and post-transcriptional regulation of GR expression. 5'-RACE, luciferase reporter assays, quantitative RT-PCR, RNA stability assays, cell signaling perturbations Molecular endocrinology (Baltimore, Md.) Medium 21527501
2015 In mouse liver under endogenous corticosterone, monomeric GR binding to a half-site motif is more prevalent than homodimer binding; GR monomers co-localize with lineage-determining transcription factors and the half-site motif drives transcription; in response to exogenous pharmacological glucocorticoids, GR dimers assemble on chromatin near ligand-activated genes concomitant with monomer evacuation from sites near repressed genes. ChIP-exo in mouse liver and primary macrophages, in vivo pharmacological GC treatment Genome research High 25957148
2016 Three novel heterozygous NR3C1 missense mutations (R477S, R477S in DBD; Y478C in DBD; L672P in LBD) cause generalized glucocorticoid resistance: DBD mutants (R477S, Y478C) show impaired nuclear translocation and reduced GRE recruitment (ChIP); L672P cannot bind glucocorticoids, is exclusively cytoplasmic, and is degradation-prone; structural modelling revealed specific loss of DNA-hydrogen bonds (R477S), destabilized DBD (Y478C), and disrupted H8-helix (L672P). Dexamethasone binding assay (Kd), nuclear translocation assay, ChIP, transactivation assay, 3D structural modelling Human mutation High 27120390
2019 KDM1A (LSD1) is an integral component of the nuclear GR complex; GR modulates KDM1A-catalyzed H3K4 progressive demethylation by limiting the loss of H3K4me1 (preserving mono-methyl while removing di-methyl marks); in cells, KDM1A removes preprogrammed H3K4me2 at GR binding sites while leaving H3K4me1, and blocking KDM1A catalytic activity prevents H3K4me2 removal, severely impairs GR chromatin binding, and dysregulates GR-targeted genes. Biochemical purification of nuclear GR complex, in vitro cell-free demethylase assay, ChIP-seq, pharmacological inhibition of KDM1A Cell reports High 31216473
2019 Deletion of Cdk5 in macrophages attenuates GR phosphorylation at serine 211 after dexamethasone treatment but paradoxically increases expression of the GR anti-inflammatory target gene Dusp1/Mkp1; Mkp1 activity decreases p38 MAPK activation and iNos expression, reducing nitric oxide production; Cdk5 thus modulates GR-dependent anti-inflammatory gene regulation in macrophages. Conditional Cdk5 knockout macrophages, Western blot (pSer211-GR), qRT-PCR, NO assay, roscovitine pharmacology Frontiers in immunology Medium 31354714
2021 Cryo-EM structure of the GR-loading complex (GR–Hsp90–Hsp70–Hop) revealed that two Hsp70 molecules are present: one delivers GR to Hsp90 and the other scaffolds Hop; GR is partially unfolded and recognized through an extended binding pocket composed of Hsp90, Hsp70, and Hop; Hop contacts all components including GR and poises Hsp90 for ATP hydrolysis; this structure defines the molecular mechanism of GR loading and inactivation by the chaperone system. Cryo-electron microscopy structure determination Nature High 34937942
2021 Cryo-EM structure of the GR-maturation complex (GR–Hsp90–p23) revealed that the GR ligand-binding domain is restored to a folded, ligand-bound conformation while being threaded through the Hsp90 lumen; p23 directly stabilizes native GR via its C-terminal helix, resulting in enhanced ligand binding; this contrasts with the unfolded conformation of GR in the loading complex, establishing the complete chaperone cycle for GR. Cryo-electron microscopy structure determination, ligand-binding assay Nature High 34937936
2021 In skeletal muscle, GR binds to numerous enhancers in collaboration with Myod1, and this co-occupancy controls myofiber-specific gene expression; transcriptional activation by GR and Myod1 occurs through direct contacts with target gene promoters via the CpG-bound transcription factor Nrf1 and formation of Ctcf-anchored chromatin loops; GR negatively controls muscle mass and strength by down-regulating anabolic pathways in vivo. ChIP-seq, 3C/Hi-C chromatin conformation, mouse conditional GR knockout, muscle function assays Nucleic acids research High 33836079
2023 NR3C1 activation in pancreatic β-cells under glucolipotoxic conditions drives hyperactive autophagy and impaired insulin secretion; mechanistically, NR3C1 upregulates the RNA demethylase FTO, which reduces m6A modifications on mRNAs of core autophagy genes (Atg12, Atg5, Atg16l2, Atg9a), leading to excessive autophagy flux; FTO inhibition (Dac51) blocks NR3C1-driven autophagy overload and restores insulin secretion in β-cell-specific NR3C1-overexpressing mice. RNA-seq, MeRIP-seq (m6A methylome), AAV-mediated NR3C1 overexpression mouse model, FTO inhibitor treatment, GSIS assay, TEM Autophagy High 37039556
2007 STAT5A, but not STAT5B, forms a complex with GR in adipocytes; STAT5A associated with GR in the nucleus is tyrosine-phosphorylated; nuclear STAT5A/GR complex formation is regulated at distinct steps in both the cytosol and nucleus during adipogenesis and in mature adipocytes. Subcellular fractionation, co-immunoprecipitation, Western blot in 3T3-L1 and 3T3-F442A adipocytes Obesity (Silver Spring, Md.) Medium 17372307
2008 Prenatal exposure to increased maternal depressed/anxious mood is associated with increased NR3C1 methylation at a predicted NGFI-A binding site in newborn cord blood; increased methylation at this site correlates with increased salivary cortisol stress responses at 3 months, linking antenatal epigenetic programming of NR3C1 to altered HPA reactivity in infancy. Bisulfite pyrosequencing of cord blood DNA, cortisol reactivity testing at 3 months Epigenetics Medium 18536531
2012 Cortisol induces hexose-6-phosphate dehydrogenase (H6PD) expression in human amnion fibroblasts through GR; GR and the histone acetyltransferase p300 are found in the same nuclear protein complex upon cortisol stimulation (co-immunoprecipitation); ChIP shows increased GR and p300 binding to the H6PD promoter and increased H3K9 acetylation; p300 inhibition blocks H6PD induction, establishing GR–p300 co-activation and histone acetylation as required for cortisol-driven H6PD transcription. Co-immunoprecipitation, ChIP, siRNA knockdown of H6PD, pharmacological GR antagonism (RU486) and p300 inhibition (C646) Endocrinology Medium 23125313
2018 Benztropine mesylate disrupts the FKBP51/GR/Hsp90 complex in vitro and restores GR localization (nuclear translocation) in ex vivo brain slices and primary neurons from mice, overcoming FKBP51-mediated suppression of GR activity without directly activating GR. High-throughput compound screen (1280 compounds), in vitro co-IP (FKBP51/GR/Hsp90 disruption assay), immunofluorescence in brain slices/neurons ACS chemical biology Medium 29893552
2022 Ahi1 regulates nuclear translocation of GR upon stress; GR acts as a transcription factor binding to glucocorticoid response elements in the ERβ promoter and inhibits ERβ transcription; reduced ERβ leads to decreased TPH2 expression and lower serotonin production; this Ahi1/GR/ERβ/TPH2 axis underlies depression-like behaviors in male mice and contributes to sex differences in serotonin production. Western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, rescue experiments in Ahi1 KO mice Cell communication and signaling : CCS Medium 35643536
2017 Dexamethasone activates GR to induce Fgf21 expression in mouse liver and human hepatoma cells via PXR-independent GR signaling; GR silencing (siRNA) or antagonism (RU486) attenuates DEX-induced Fgf21; ChIP-qPCR shows increased GR binding to cis-regulatory elements in the Fgf21/FGF21 promoter; DEX pretreatment ameliorates acetaminophen-induced liver injury in wild-type but not Fgf21-null mice, demonstrating that GR-driven Fgf21 induction mediates hepatoprotection. siRNA knockdown, GR antagonist, ChIP-qPCR, Fgf21-null mouse model, luciferase reporter assay Toxicology Medium 28088388
2024 NR3C1 activated by a super-enhancer forms liquid-liquid phase separation condensates (observed by FRAP) and, together with the Mediator complex, promotes SE-related gene transcription associated with 5-FU resistance in gastric cancer; NR3C1 and super-enhancers co-bind 5-FU-resistance gene loci (CUT&Tag); NR3C1 knockdown or inhibition (Cort108297) reduces downstream 5-FU-related target gene expression and increases 5-FU sensitivity in PDOs and PDX models. ChIP-seq, CUT&Tag, FRAP (phase separation), siRNA knockdown, PDO/PDX pharmacological treatment Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39731339
2024 NR3C1 is a direct transcriptional regulator of ferroptosis-related genes HSPB1 and NCOA4 in glioblastoma; ginsenoside Rg5 activates the ferroptosis pathway by targeting NR3C1, which modulates HSPB1 and NCOA4 expression; intracranial xenograft assays confirmed that NR3C1-driven ferroptosis activation inhibits glioblastoma progression. RNA-seq, intersection analysis (differentially expressed genes vs. predicted NR3C1 targets), ChIP/reporter validation of NR3C1–HSPB1/NCOA4 axis, intracranial xenograft Phytomedicine : international journal of phytotherapy and phytopharmacology Low 38640858

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature neuroscience 2108 19234457
1985 Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1623 2867473
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature genetics 1381 10391209
1991 Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 1238 1865905
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2010 Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Science signaling 1039 20124551
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2008 Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 964 18536531
2005 HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Molecular cell 954 15916966
2017 Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science (New York, N.Y.) 934 28473536
1994 Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proceedings of the National Academy of Sciences of the United States of America 898 8290595
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2001 The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nature cell biology 829 11146632
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1995 Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Molecular and cellular biology 695 7823959
2002 Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 670 12151000
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2009 DNA binding site sequence directs glucocorticoid receptor structure and activity. Science (New York, N.Y.) 545 19372434
1996 Functional interactions between Stat5 and the glucocorticoid receptor. Nature 544 8878484
1993 A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. The EMBO journal 544 8223438
2000 Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Molecular and cellular biology 536 10958685
2005 Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 525 16143103
2004 FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. The Journal of biological chemistry 523 15591061
1995 Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans. The Journal of clinical investigation 522 7769088
2005 Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. The Journal of experimental medicine 495 16380507
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2011 Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature 467 22170608
2014 Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer. Nature 312 25156255
2015 Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience and biobehavioral reviews 255 26073068
2001 A Gr receptor is required for response to the sugar trehalose in taste neurons of Drosophila. Nature neuroscience 212 11704765
2015 Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics 188 25875334
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 163 34937942
2020 C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy. Science translational medicine 156 32878979
2020 Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway. Circulation research 153 33334122
2015 Genomic redistribution of GR monomers and dimers mediates transcriptional response to exogenous glucocorticoid in vivo. Genome research 137 25957148
2009 Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity. Biochemical and biophysical research communications 132 19248771
2006 ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cellular oncology : the official journal of the International Society for Cellular Oncology 123 17167179
2021 Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism. Nature 114 34937936
2005 GR and HMGB1 interact only within chromatin and influence each other's residence time. Molecular cell 101 15808513
2005 The Y chromosome gr/gr subdeletion is associated with male infertility. Molecular human reproduction 91 16123079
2018 Proteomics and C9orf72 neuropathology identify ribosomes as poly-GR/PR interactors driving toxicity. Life science alliance 87 30456350
2020 Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19. Frontiers in immunology 80 32983174
2004 High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Human reproduction (Oxford, England) 78 15513974
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
2009 Y chromosome gr/gr deletions are a risk factor for low semen quality. Human reproduction (Oxford, England) 59 19602516
2016 Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy. Pharmacology & therapeutics 57 27288728
2008 Understanding the multiple functions of Gr-1(+) cell subpopulations during microbial infection. Immunologic research 57 18193362
2004 Getting a GR(i)P on oligodendrocyte development. Developmental biology 57 14697351
2014 Glucocorticoid regulation of lung development: lessons learned from conditional GR knockout mice. Molecular endocrinology (Baltimore, Md.) 55 25535891
2018 NR3C1 hypermethylation in depressed and bullied adolescents. Translational psychiatry 54 29921868
2014 Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior. Psychoneuroendocrinology 51 25459891
2006 Study of AZFc partial deletion gr/gr in fertile and infertile Japanese males. Journal of human genetics 51 16900294
2020 Increased methylation of NR3C1 and SLC6A4 is associated with blunted cortisol reactivity to stress in major depression. Neurobiology of stress 49 33344725
2002 Inactivation of the GR in the nervous system affects energy accumulation. Endocrinology 49 12021198
2013 Nuclear receptors in inflammation control: repression by GR and beyond. Molecular and cellular endocrinology 48 23623868
2022 Crosstalk between p38 MAPK and GR Signaling. International journal of molecular sciences 47 35328742
2006 No association found between gr/gr deletions and infertility in Brazilian males. Molecular human reproduction 44 16597640
2023 NR3C1/Glucocorticoid receptor activation promotes pancreatic β-cell autophagy overload in response to glucolipotoxicity. Autophagy 42 37039556
2008 Effects of serotonin depletion on the hippocampal GR/MR and BDNF expression during the stress adaptation. Behavioural brain research 41 18601957
2020 Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism. Frontiers in endocrinology 40 33133019
2018 Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD. ACS chemical biology 40 29893552
2019 eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated ALS. Acta neuropathologica communications 38 31023341
2016 FKBP5 mRNA Expression Is a Biomarker for GR Antagonism. The Journal of clinical endocrinology and metabolism 38 27459525
2016 Three Novel Heterozygous Point Mutations of NR3C1 Causing Glucocorticoid Resistance. Human mutation 36 27120390
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) 35 34825505
2015 Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation. Biology of reproduction 35 26085523
2012 Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland. Molecular biology reports 35 23073785
2010 Features of constitutive gr/gr deletion in a Japanese population. Human reproduction (Oxford, England) 35 20663794
2006 Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity. BMC medical genetics 35 16725041
2017 Hippocampal NR3C1 DNA methylation can mediate part of preconception paternal stress effects in rat offspring. Behavioural brain research 34 28212940
2011 Hippocampal GR expression is increased in elderly depressed females. Neuropharmacology 34 21945289
2015 Glucocorticoid receptor gene (NR3C1) promoter is hypermethylated in Thai females with major depressive disorder. Genetics and molecular research : GMR 33 26782558
2011 A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR and PPARs. PPAR research 33 21941526
2015 Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study. Journal of affective disorders 32 25889020
2022 The long winding road to the safer glucocorticoid receptor (GR) targeting therapies. Oncotarget 31 35198100
2016 HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome. Diabetes/metabolism research and reviews 31 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 29 31216473
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
2021 Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation. Scientific reports 28 33762648
2015 Beneficial effects of the β-secretase inhibitor GRL-8234 in 5XFAD Alzheimer's transgenic mice lessen during disease progression. Current Alzheimer research 28 25523425
2022 Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors. Cell communication and signaling : CCS 27 35643536
1991 A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp. Biochemical genetics 27 1679325
2021 Myod1 and GR coordinate myofiber-specific transcriptional enhancers. Nucleic acids research 26 33836079
2020 GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy. BMC cancer 25 32106831
2020 DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia. Journal of molecular neuroscience : MN 25 32281042
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
2014 Purification and characterization of detergent-compatible protease from Aspergillus terreus gr. 3 Biotech 24 28324360
2021 Gestational cadmium exposure impairs placental angiogenesis via activating GC/GR signaling. Ecotoxicology and environmental safety 23 34411824
2008 RXFP1-inactive relaxin activates human glucocorticoid receptor: further investigations into the relaxin-GR pathway. Regulatory peptides 23 19101597
2024 Ginsenoside Rg5 inhibits glioblastoma by activating ferroptosis via NR3C1/HSPB1/NCOA4. Phytomedicine : international journal of phytotherapy and phytopharmacology 22 38640858
2019 Cdk5 Deletion Enhances the Anti-inflammatory Potential of GC-Mediated GR Activation During Inflammation. Frontiers in immunology 22 31354714
2016 Medical morbidities and DNA methylation of NR3C1 in preterm infants. Pediatric research 22 27653086
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
2014 NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association. Arquivos brasileiros de endocrinologia e metabologia 21 24728165
2021 Effect of 3 NR3C1 Mutations in the Pathogenesis of Pituitary ACTH Adenoma. Endocrinology 20 34427636
2020 Isovaleroylbinankadsurin A ameliorates cardiac ischemia/reperfusion injury through activating GR dependent RISK signaling. Pharmacological research 20 32422343
2013 Tamoxifen inhibits macrophage FABP4 expression through the combined effects of the GR and PPARγ pathways. The Biochemical journal 20 23805908
2007 The modulation of STAT5A/GR complexes during fat cell differentiation and in mature adipocytes. Obesity (Silver Spring, Md.) 20 17372307
2019 DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex. Infant mental health journal 19 31066465
2021 Role of NR3C1 and SLC6A4 methylation in the HPA axis regulation in burnout. Journal of affective disorders 18 34509065
2021 Perinatal stress and methylation of the NR3C1 gene in newborns: systematic review. Epigenetics 18 34519616
2019 Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age. Frontiers in behavioral neuroscience 18 30804765
2018 GR-regulating Serine/Threonine Kinases: New Physiologic and Pathologic Implications. Trends in endocrinology and metabolism: TEM 18 29501228
2018 Engineering Lactobacillus rhamnosus GG and GR-1 to express HIV-inhibiting griffithsin. International journal of antimicrobial agents 17 30040991
2017 Activation of GR but not PXR by dexamethasone attenuated acetaminophen hepatotoxicities via Fgf21 induction. Toxicology 17 28088388
2012 Involvement of GR and p300 in the induction of H6PD by cortisol in human amnion fibroblasts. Endocrinology 17 23125313
2024 Super-enhancer Activates Master Transcription Factor NR3C1 Expression and Promotes 5-FU Resistance in Gastric Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 39731339
2021 Clinical Correlates of the NR3C1 Gene Methylation at Various Stages of Psychosis. The international journal of neuropsychopharmacology 16 33284958
2021 Association Between NR3C1 Mutations and Glucocorticoid Resistance in Children With Acute Lymphoblastic Leukemia. Frontiers in pharmacology 16 33854435
2021 p53 Transactivation Domain Mediates Binding and Phase Separation with Poly-PR/GR. International journal of molecular sciences 16 34768862
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
2010 Diagnosis of the gr/gr Y chromosome microdeletion does not help in the treatment of infertile American men. The Journal of urology 16 21074808
2005 Novel genetic polymorphisms in the NR3C1 (glucocorticoid receptor) gene in a Japanese population. Drug metabolism and pharmacokinetics 16 15770078
2022 Hypothalamic NR3C1 DNA methylation in rats exposed to prenatal stress. Molecular biology reports 15 35661969
2015 Diabetes Inhibits Gr-1+ Myeloid Cell Maturation via Cebpa Deregulation. Diabetes 15 26324181
2013 Identification of GR and TrxR systems in Setaria cervi: Purification and characterization of glutathione reductase. Parasitology international 15 23305756
2013 Transcript variants of the porcine glucocorticoid receptor gene (NR3C1). General and comparative endocrinology 15 23684967
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
2017 Activation of intestinal GR-FXR and PPARα-UGT signaling exacerbates ibuprofen-induced enteropathy in mice. Archives of toxicology 13 29222744
2016 Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog. Reproduction (Cambridge, England) 13 27530348