ArticleMolecular endocrinology (Baltimore, Md.)2008
Glucocorticoid regulation of the promoter of 11beta-hydroxysteroid dehydrogenase type 1 is indirect and requires CCAAT/enhancer-binding protein-beta.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 81 citations in OpenAlex.
- Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.Endocrine journal · 2026Review
- Glucocorticoid activates STAT3 and NF-κB synergistically with inflammatory cytokines to enhance the anti-inflammatory factor TSG6 expression in mesenchymal stem/stromal cells.Cell death & disease · 2024Article
- Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.The Journal of clinical endocrinology and metabolism · 2023Article
- C/EBPδ drives key endocrine signals in the human amnion at parturition.Clinical and translational medicine · 2021Article
- 11β-hydroxysteroid dehydrogenases: A growing multi-tasking family.Molecular and cellular endocrinology · 2021Review
- The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance.Biomedicines · 2020Article
- Decreased 11β-hydroxysteroid dehydrogenase 1 in lungs of steroid receptor coactivator (Src)-1/-2 double-deficient fetal mice is caused by impaired glucocorticoid and cytokine signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in αT3-1 and LβT2 Gonadotroph Cells.Biology · 2019Article
- The ratio of 11β-hydroxysteroid dehydrogenase 1/11β-hydroxysteroid dehydrogenase 2 predicts glucocorticoid response in nasal polyps.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2019Article
- Social defeat stimulates local glucocorticoid regeneration in lymphoid organs.Endocrine connections · 2018Article
- 11β-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation.Brain, behavior, and immunity · 2018Article
- Changes in 11β-Hydroxysteroid Dehydrogenase and Glucocorticoid Receptor Expression in Kawasaki Disease.Korean circulation journal · 2017Article
- Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium.Journal of molecular endocrinology · 2017Review
- 11β-Hydroxysteroid Dehydrogenase Type 1 Is Expressed in Neutrophils and Restrains an Inflammatory Response in Male Mice.Endocrinology · 2016Article
- Sex-Dependent effects of developmental arsenic exposure on methylation capacity and methylation regulation of the glucocorticoid receptor system in the embryonic mouse brain.Toxicology reports · 2015Article
- Diurnal and stress-induced intra-hippocampal corticosterone rise attenuated in 11β-HSD1-deficient mice: a microdialysis study in young and aged mice.The European journal of neuroscience · 2015Article
- Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women.International journal of obesity (2005) · 2015Article
- Intrahippocampal glucocorticoids generated by 11β-HSD1 affect memory in aged mice.Neurobiology of aging · 2015Article
- TNFα-mediated Hsd11b1 binding of NF-κB p65 is associated with suppression of 11β-HSD1 in muscle.The Journal of endocrinology · 2014Article
- Regulation of 11β-hydroxysteroid dehydrogenase type 1 and 7α-hydroxylase CYP7B1 during social stress.PloS one · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert 11keto-glucocorticoids to active 11beta-hydroxy forms, thereby amplifying intracellular glucocorticoid action. Up-regulation of 11beta-HSD1 in adipose tissue and liver is of pathogenic importance in metabolic syndrome. However, the mechanisms controlling 11beta-HSD1 transcription are poorly understood. Glucocorticoids themselves potently increase 11beta-HSD1 expression in many cells, providing a potential feed-forward system to pathology. We have investigated the molecular mechanisms by which glucocorticoids regulate transcription of 11beta-HSD1, exploiting an A549 cell model system in which endogenous 11beta-HSD1 is expressed and is induced by dexamethasone. We show that glucocorticoid induction of 11beta-HSD1 is indirect and requires new protein synthesis. A glucocorticoid-responsive region maps to between -196 and -88 with respect to the transcription start site. This region contains two binding sites for CCAAT/enhancer-binding protein (C/EBP) that together are essential for the glucocorticoid response and that bind predominantly C/EBPbeta, with C/EBPdelta present in a minority of the complexes. Both C/EBPbeta and C/EBPdelta are rapidly induced by glucocorticoids in A549 cells, but small interfering RNA-mediated knockdown shows that only C/EBPbeta reduction attenuates the glucocorticoid induction of 11beta-HSD1. Chromatin immunoprecipitation studies demonstrated increased binding of C/EBPbeta to the 11beta-HSD1 promoter in A549 cells after glucocorticoid treatment. A similar mechanism may apply in adipose tissue in vivo where increased C/EBPbeta mRNA levels after glucocorticoid treatment were associated with increased 11beta-HSD1 expression. C/EBPbeta is a key mediator of metabolic and inflammatory signaling. Positive regulation of 11beta-HSD1 by C/EBPbeta may link amplification of glucocorticoid action with metabolic and inflammatory pathways and may represent an endogenous innate host-defense mechanism.
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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.