ArticleMolecular endocrinology (Baltimore, Md.)2010
Discovery of glucocorticoid receptor-beta in mice with a role in metabolism.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 127 citations in OpenAlex.
- STING pathway contributes to Steroid-Hyporesponsive Lung Inflammation in DSS-induced colitis mice model.PloS one · 2026Article
- Cedrol mitigates hepatic lipid accumulation and adipocyte hypertrophy induced by corticosteroids through the inhibition of glucocorticoid receptor activity.Scientific reports · 2025Article
- Mifepristone alone and in combination with scAAV9-SMN1 gene therapy improves disease phenotypes in SmnScientific reports · 2025Article
- Vitamin D3 suppresses NLRP3 inflammasome pathway and enhances steroid sensitivity in a neutrophilic steroid hyporesponsive asthma mouse model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Role of glucocorticoid receptor expression in Chronic Chagas Cardiomyopathy: implications for inflammation and cardiac hypertrophy.Frontiers in endocrinology · 2025Article
- Activation of the Nrf2/HO-1 pathway restores N-acetylcysteine-induced impairment of the hypothalamus-pituitary-adrenal axis negative feedback by up-regulating GRα expression and down-regulating GRβ expression into pituitary glands.Frontiers in endocrinology · 2025Article
- Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.Prostaglandins & other lipid mediators · 2024Review
- Mineralocorticoid Receptor Antagonism Reduces Inflammatory Pain Measures in Mice Independent of the Receptors on Sensory Neurons.Neuroscience · 2024Article
- Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.eLife · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Context is key: glucocorticoid receptor and corticosteroid therapeutics in outcomes after traumatic brain injury.Frontiers in cellular neuroscience · 2024Review
- Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.bioRxiv : the preprint server for biology · 2023Article
- Complete Tolerogenic Adjuvant Stimulates Regulatory T Cell Response to Immunization.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Expression and clinicopathological significance of glucocorticoid receptor, SGK1, and NDRG1 in hormone-naïve prostate carcinoma.Medical molecular morphology · 2022Article
- Interactions between nuclear receptors glucocorticoid receptor α and peroxisome proliferator-activated receptor α form a negative feedback loop.Reviews in endocrine & metabolic disorders · 2022Review
- Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism.International journal of molecular sciences · 2022Article
- Class 3 phosphoinositide 3-kinase promotes hepatic glucocorticoid receptor stability and transcriptional activity.Acta physiologica (Oxford, England) · 2022Article
- Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Nuclear Receptors in Energy Metabolism.Advances in experimental medicine and biology · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Glucocorticoid hormones control diverse physiological processes, including metabolism and immunity, by activating the major glucocorticoid receptor (GR) isoform, GRalpha. However, humans express an alternative isoform, human (h)GRbeta, that acts as an inhibitor of hGRalpha to produce a state of glucocorticoid resistance. Indeed, evidence exists that hGRbeta contributes to many diseases and resistance to glucocorticoid hormone therapy. However, rigorous testing of the GRbeta contribution has not been possible, because rodents, especially mice, are not thought to express the beta-isoform. Here, we report expression of GRbeta mRNA and protein in the mouse. The mGRbeta isoform arises from a distinct alternative splicing mechanism utilizing intron 8, rather than exon 9 as in humans. The splicing event produces a form of beta that is similar in structure and functionality to hGRbeta. Mouse (m)GRbeta has a degenerate C-terminal region that is the same size as hGRbeta. Using a variety of newly developed tools, such as a mGRbeta-specific antibody and constructs for overexpression and short hairpin RNA knockdown, we demonstrate that mGRbeta cannot bind dexamethasone agonist, is inhibitory of mGRalpha, and is up-regulated by inflammatory signals. These properties are the same as reported for hGRbeta. Additionally, novel data is presented that mGRbeta is involved in metabolism. When murine tissue culture cells are treated with insulin, no effect on mGRalpha expression was observed, but GRbeta was elevated. In mice subjected to fasting-refeeding, a large increase of GRbeta was seen in the liver, whereas mGRalpha was unchanged. This work uncovers the much-needed rodent model of GRbeta for investigations of physiology and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.