NR3C1 (Ab-226) Antibody
Description
Target Information: The Glucocorticoid Receptor (NR3C1)
The target of NR3C1 (Ab-226) Antibody is the glucocorticoid receptor, a critical nuclear receptor encoded by the NR3C1 gene located on chromosome 5 in humans . This receptor serves as a central mediator in various physiological processes and plays a pivotal role in stress response mechanisms.
Structure and Function
The glucocorticoid receptor is widely distributed throughout the body and functions primarily as a ligand-dependent transcription factor. Upon binding to glucocorticoids such as cortisol, the receptor undergoes conformational changes that allow it to translocate from the cytoplasm to the nucleus . Within the nucleus, it can either activate or repress gene transcription by binding to specific DNA sequences known as glucocorticoid response elements (GREs).
Physiological Significance
NR3C1 is intricately involved in numerous bodily functions including:
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Metabolism regulation
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Immune system modulation
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Stress adaptation
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Cellular proliferation and differentiation
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Anti-inflammatory responses
The receptor modulates gene transcription by binding to hormones like cortisol and can inhibit pro-inflammatory pathways by preventing the translocation of other transcription factors from the cytosol into the nucleus . This mechanism is crucial for understanding the anti-inflammatory effects of glucocorticoids in clinical settings.
Phosphorylation Sites and Their Significance
The NR3C1 (Ab-226) Antibody specifically targets the phosphorylation sites at serine residues 226, 234, and 246 of the glucocorticoid receptor . This specificity is particularly important as phosphorylation at these sites regulates receptor function and activity.
Serine 226 Phosphorylation
Phosphorylation at serine 226 is particularly noteworthy as it has been associated with altered receptor function. The anti-GR (phospho-S226) antibody specifically detects NR3C1 when phosphorylated at this position . This modification has been linked to:
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Altered nuclear translocation dynamics
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Modified transcriptional activity
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Changes in target gene expression patterns
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Potential involvement in pathological states
Research indicates that phosphorylation status at these serine residues can significantly influence the receptor's ability to mediate glucocorticoid signaling, making antibodies targeting these sites valuable research tools.
Applications in Research
NR3C1 (Ab-226) Antibody has demonstrated utility across multiple experimental applications, providing researchers with a versatile tool for investigating glucocorticoid receptor biology and function.
Western Blotting
The antibody is recommended for western blot applications at dilutions of 1:500-1:3000 or 1:500-1:1000 . This application allows researchers to detect and quantify NR3C1 protein expression in various tissue and cell lysates. The expected molecular weight of the glucocorticoid receptor is approximately 86 kDa, though multiple isoforms may be detected depending on the specific tissue or cell type being analyzed.
Immunohistochemistry
For immunohistochemical applications, the recommended dilution range is 1:50-1:200 or 1:50-1:100 . This technique enables the visualization of glucocorticoid receptor distribution within tissue sections, providing valuable insights into expression patterns across different cell types and in response to various physiological or pathological conditions.
ELISA
The antibody is also validated for enzyme-linked immunosorbent assay (ELISA) applications, allowing for quantitative detection of the glucocorticoid receptor in solution-based samples .
Research Significance and Findings
The glucocorticoid receptor has been extensively studied in relation to various physiological and pathological conditions. Antibodies targeting specific phosphorylation sites, such as NR3C1 (Ab-226) Antibody, have contributed significantly to this body of research.
Genetic Polymorphisms and Clinical Correlations
Research has identified several single nucleotide polymorphisms (SNPs) within the NR3C1 gene that may influence receptor function and disease susceptibility. A study examining SNPs in the NR3C1 gene found significant associations with major depressive disorder (MDD) . Specifically:
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SNP NR3C1-1 in the promoter region showed a significant association with MDD in a Belgian sample
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SNP R23K in exon 2 showed a significant association with MDD in a Swedish sample
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Haplotype analysis revealed that haplotypes containing these SNPs showed evidence for association with MDD
These findings suggest that polymorphisms in the 5' region of the NR3C1 gene may play a role in genetic vulnerability for major depressive disorder, highlighting the importance of studying glucocorticoid receptor function in psychiatric conditions .
Antibody Validation in Experimental Models
The NR3C1 (Ab-226) Antibody has been validated in multiple experimental models. For instance, immunohistochemical analysis using anti-NR3C1 antibodies has successfully detected the receptor in paraffin-embedded sections of mouse cardiac muscle tissue, demonstrating the antibody's utility in animal model research .
Avoiding Degradation
Repeated freeze-thaw cycles should be avoided as they can lead to protein denaturation and loss of antibody activity. If frequent use is anticipated, aliquoting the antibody into smaller volumes before freezing is recommended to minimize freeze-thaw cycles .
Comparison with Related NR3C1 Antibodies
Several antibodies targeting the glucocorticoid receptor are commercially available, each with specific characteristics and applications. The NR3C1 (Ab-226) Antibody distinguishes itself through its targeted recognition of specific phosphorylation sites.
The choice between these antibodies depends on the specific research question and experimental design. For studies focusing on phosphorylation-dependent regulation of the glucocorticoid receptor, NR3C1 (Ab-226) Antibody offers specific advantages due to its ability to recognize multiple phosphorylation sites.
Product Specs
Target Background
- Relaxin-GR signaling plays a role in hepatocellular protection against ischemia-reperfusion stress in liver transplantation. PMID: 29350771
- The Bcl1 G/G polymorphism of the glucocorticoid receptor gene is associated with bronchial asthma complicated by obesity. PMID: 30480407
- Topical mevastatin accelerates wound closure by promoting epithelialization through multiple mechanisms: modulation of GR ligands and induction of the long noncoding RNA Gas5, leading to c-Myc inhibition. PMID: 29158265
- Alpha-Viniferin (KCV) inhibits the activation of the glucocorticoid receptor (GR) signaling pathway in non-androgen-dependent Prostate cancer (PCa) cells. KCV induces cancer cell apoptosis through AMP-Activated Protein Kinases-mediated activation of autophagy, and inhibits GR expression in castration-resistant prostate cancer (CRPC). PMID: 29904891
- Genotype frequencies for the NR3C1 polymorphisms in patients and controls were distributed as follows: rs6191 TT 37 : 56, GT 178 : 36, GG 332 : 609; rs6196 AA 483 : 905, AG 66 : 118, GG 2 : 4; rs10482614 GG 493 : 916, AG 61 : 108, AA 1 : 4; and rs72557310 AG 27 : 65, GG 3 : 0, AA 525 : 964. No significant differences were observed in genotype frequency or allele distributions between cases and controls. PMID: 29381656
- The Glucocorticoid Receptor positively regulates transcription of FNDC5 in the liver. PMID: 28240298
- Polymorphisms in the NR3C1 gene are associated with sensitivity to glucocorticoids and may contribute to glucose abnormalities in Acute Lymphoblastic Leukemia. PMID: 29802709
- NR3C1 methylation moderates the effect of maternal support during stress on anxious attachment development 18 months later. Children who experienced more stress and less maternal support exhibited increased anxious attachment when their NR3C1 gene was highly methylated. This effect was not explained by the children's level of psychopathology. PMID: 29058930
- Meta-analysis demonstrated that homozygous mutation of NR3C1 rs41423247 was associated with Depression. PMID: 30278546
- This review focuses on earlier findings on the pathophysiology of GR signaling and presents criteria for identifying novel NR3C1 mutations in selected patients. [review] PMID: 29685454
- The study indicates that GR genetic polymorphisms may play a significant role in the pathogenesis and development of systemic lupus erythematosus. PMID: 28984075
- Meta-analysis revealed a significant association between the BclI NR3C1 polymorphisms and asthma in adults. PMID: 29729712
- This study shows genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. PMID: 29738565
- There was no significant association between different genotypes and alleles of Glucocorticoid Receptor of rs6195, rs6189/rs6190 variants, and response to fluoxetine (p=0.213 and 0.99, respectively). PMID: 28641498
- NR3C1 gene polymorphisms are significantly associated with the response to glucocorticoids. PMID: 29207898
- No clear evidence suggests that the analyzed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases, although the minor G allele of rs41423247 may be protective among Caucasians (review and meta-analysis). PMID: 29526633
- Analyses demonstrated a trend in the association between maternal trait anxiety and depression symptoms with placental gene expression of NR3C1. A significant interaction with maternal ethnicity was found. In Caucasians only, prenatal trait anxiety and depressive symptoms were associated with an increase in placental NR3C1 expression, and prenatal life events were associated with a downregulation of HSD11B2. PMID: 29100173
- Ten single nucleotide polymorphisms (SNPs) on the NR3C1 gene (rs10482682, rs33389, rs10482633, rs10515522, rs2963156, rs4128428, rs9324918, rs41423247, rs6189, rs10052957) were genotyped. Haplotype analyses revealed significant effects of NR3C1 (p = 0.011) on cortisol stress response. Neither NR3C1 haplotype nor NR3C2 haplotype was associated with reasoning abilities. PMID: 29100174
- This study described the cellular localization of the glucocorticoid receptor in the human adult and fetal testis and provided evidence of an association between semen quality and a genetic polymorphism BclI (rs41423247) in the NR3C1 gene. PMID: 28992366
- Results indicate that maltreated children exhibit higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. PMID: 29162170
- Children with early-onset maltreatment evidence significant hypermethylation compared to nonmaltreated children. Additionally, hypermethylation of NR3C1 is linked with various negative child outcomes, including greater emotional lability-negativity, higher levels of ego undercontrol, more externalizing behavior, and greater depressive symptoms. PMID: 29162187
- This study evaluated whether associations between early adversity and brain responses to dynamic facial expressions in early adulthood varied based on regional differences in the expression of NR3C1. The strongest associations between adversities and BOLD response to fearful faces were observed in brain regions with higher NR3C1 mRNA expression levels. The highest expression of NR3C1 is found in the occipital region and the lowest in temporal regions. PMID: 28612935
- This study defines a distinct GRgamma-driven signaling network, including the identification of GRgamma-specific subcellular trafficking, target gene selection, and engagement of interacting proteins. Both transcriptome and protein interactome data suggest a role for GRgamma in directing mitochondrial function. Indeed, GRgamma expression increased mitochondrial mass, basal respiration, and ATP generation. PMID: 27226058
- This study examined single nucleotide polymorphisms in the human glucocorticoid receptor (NR3C1) gene with regard to susceptibility to high-altitude pulmonary edema (HAPE) in the Han Chinese population. PMID: 29587872
- In patients with adrenal incidentalomas, a 5% prevalence of heterozygous NR3C1 mutations was discovered. PMID: 29444898
- This study demonstrated that NR3C1 expression levels are related to major depressive disorder and mediate the effect of childhood maltreatment history on the risk of developing major depressive disorder. PMID: 28384542
- This study demonstrated increased methylation of the glucocorticoid receptor gene promoter 1F in the peripheral blood of patients with generalized anxiety disorder. PMID: 28292649
- This study suggests that SNPs in the NR3C1 gene may influence BDNF levels in crack cocaine addiction. PMID: 28237884
- This study identified a molecular signature of secreted proteins associated with AA ultraresponsiveness and sustained AR/GR signaling upon AA resistance in intermediate or minimal responders. These data will inform the development of noninvasive biomarkers predicting AA response and suggest that further inhibition along the AR/GR signaling axis may be effective only in AA-resistant patients who are intermediate or minimal responders. PMID: 27993966
- A Tri-Nucleotide Pattern in a 3' UTR Segment Affects The Activity of a Human Glucocorticoid Receptor Isoform. PMID: 27660999
- Association Between N363S and BclI Polymorphisms of the Glucocorticoid Receptor Gene (NR3C1) and Glucocorticoid Side Effects During Childhood Acute Lymphoblastic Leukemia Treatment. PMID: 28179212
- Genetic association studies in a population in Brazil: Data suggest that an SNP in NR3C1 (A3669G) is associated with appetite regulation and food preferences. Adolescents carrying the A3669G variant exhibited decreased comfort food intake. PMID: 28400302
- Results provide evidence for an association between the NR3C1-rs41423247 SNP and depression: The C minor allele of rs41423247 increased depressive symptoms during early abstinence of women with crack cocaine addiction, but it did not have effects over detoxification treatment. A slight effect of the CC genotype was shown at the late abstinence phase. The C allele of this SNP was associated with an increased number of rehospitalizations. PMID: 27397864
- No significant interaction was observed between NR3C1 and stressful life events with respect to alcohol use/misuse. PMID: 26751645
- Dehydroepiandrosterone (DHEA) and cortisol modulate SRSF9 and SRSF3 differently. Data suggest that the anti-glucocorticoid effect of DHEA, among other mechanisms, is also exerted by modulating the expression of proteins involved in the splicing of the GR pre-mRNA. PMID: 28373129
- Association between suicide and altered NR3C1 gene expression in the prefrontal cortex. PMID: 27030168
- This study identified three novel heterozygous missense NR3C1 mutations causing glucocorticoid resistance in patients with adrenal incidentalomas without Cushing's syndrome. p.R477S and p.Y478C are located in the DNA binding domain (DBD) of the glucocorticoid receptor (GR), while p.L67P is located in the ligand binding domain of GR. PMID: 27120390
- Data show that the 3' UTR of glucocorticoid receptor beta (GRbeta) is regulated by miR144. PMID: 27036026
- Except for a slightly higher risk of bronchopulmonary dysplasia (BPD) in carriers of the GRBclI variant, the glucocorticoid receptor gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of Very-Low-Birth-Weight preterm infants. PMID: 27509264
- Possible influence of the BclI C/G polymorphism (rs41423247) on hippocampal shape and integrity of the parahippocampal subdivision of the cingulum in depression. PMID: 27428087
- A woman with glucocorticoid resistance and her mother had a novel p.Arg477Cys (c.1429C>T) mutation in exon 4 of NR3C1, in the 2dzinc finger of the DNA-binding domain. Its 'in silico' functional effect was assessed using pathogenicity prediction software, being characterized as pathogenic. An unrelated patient had a novel p.His588Leufs*5 (c.1762_1763insTTAC) mutation, in exon 6, in the ligand binding domain. PMID: 27211791
- NR3C1 as an important gene of the hypothalamic-pituitary-adrenal axis seems to be particularly relevant for the pathophysiology of ADHD combined with comorbid CD. PMID: 27741480
- A significant protein-protein interaction between GR and CHOP, (GR-CHOP heterocomplex formation) under endoplasmic reticulum stress conditions, is reported. PMID: 27496643
- Childhood Maltreatment and MDD are both associated with altered DNA methylation levels in the NR3C1 promoter region; however, the location and direction of effects differ between the two exposures. PMID: 27475889
- This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety, and substance-use disorders in adults. PMID: 27378548
- Genetic association studies in a racially diverse population in North Carolina: Data suggest that an SNP in NR3C1 (rs6191, G3134T, “glucocorticoid receptor beta”) is associated with an altered gene expression profile in primary macrophages; the minor allele frequency is 74% with a higher prevalence in Caucasian non-Hispanic participants. PMID: 28759007
- Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair, and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels. PMID: 27653086
- The G-allele was associated with childhood overweight, depressive disorder comorbidity, and diagnostic instability. G-allele carriers reporting childhood overweight showed greater frequency of subjective binge eating and emotional eating. PMID: 27400218
- The haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR rs1800445 and MR (NR3C2) rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population. PMID: 28686058
- The Glucocorticoid Receptor (GR) is recruited to activator protein-1 (AP-1) target genes in a DNA-binding-dependent manner. PMID: 28591827
