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cAMP activates transcription of the human glucocorticoid receptor gene promoter
Abstract
Glucocorticoids and cAMP regulate, either in a synergistic or additive fashion, the transcription of multiple genes, although some antagonistic effects of dexamethasone on cAMP-activated transcription have been described. The increased glucocorticoid receptor (GR) mediated response of some cell types, as a result of augmented cAMP, has been considered to be mainly due to an increased stability of GR mRNA, although other plausible explanations should not be ruled out. We studied the possibility that GR transcription itself could be affected by cAMP levels. HeLa cells were transfected with human GR (hGR) promoter constructs and their transcriptional activity determined after inducing a cAMP increase with forskolin. We found that forskolin almost doubled the transcriptional activity of the promoter construct spanning -2995 to +38 of the hGR, whereas no significant variations were observed with shorter chimeras containing sequences downstream -979. Shift mobility showed binding of CREB in vitro to a putative cAMP responsive element located at -1000, suggesting that hGR may be upregulated by cAMP at the transcriptional level, thus adding a new mechanism ascribable to this second messenger, which in conjunction with the cAMP-induced GR mRNA increased stability, would lead to a more precise control of the amount of GR protein within the cell.
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PKA agonists, including forskolin and 8-Br-cAMP, increase GR mRNA stability and GR mRNA levels and enhance GR transcription and function.
“PKA agonists, including forskolin and 8-Br-cAMP, increase GR mRNA stability and GR mRNA levels and enhance GR transcription and function.109,110”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [109]
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Metadata
- Authors
- Peñuelas, I., Encı́o, I. J., López-Moratalla, N., & Santiago, E.
- Affiliations
- Universidad de Navarra (ES)
- Universidad Pública de Navarra (UPNA) (ES)
- Corresponding author
- Peñuelas, Iván
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 67
- Issue
- 2
- Pages
- 89-94
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2042906229
- Cited by
- 27
- References
- 22
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2020: 3 · 2013: 1 · 2012: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoid receptor, cyclic AMP, transcriptional regulation, forskolin, CREB, cAMP response element, HeLa cells, second messenger signaling
- MeSH terms
- Cyclic AMP, Colforsin, Glucocorticoids, HeLa Cells, Humans, Plasmids, Promoter Regions, Genetic, Receptors, Glucocorticoid, Transfection, Transcriptional Activation
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