Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem
For over 70 years, the unique anti-inflammatory properties of glucocorticoids (GCs), which mediate their effects via the ligand-activated transcription factor, the glucocorticoid receptor alpha (GRα), have allowed for the use of these steroid hormones in the treatment of various autoimmune and infla...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2529 |
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| author | Lee-Maine L. Spies Nicolette J. D. Verhoog Ann Louw |
| author_facet | Lee-Maine L. Spies Nicolette J. D. Verhoog Ann Louw |
| author_sort | Lee-Maine L. Spies |
| collection | DOAJ |
| description | For over 70 years, the unique anti-inflammatory properties of glucocorticoids (GCs), which mediate their effects via the ligand-activated transcription factor, the glucocorticoid receptor alpha (GRα), have allowed for the use of these steroid hormones in the treatment of various autoimmune and inflammatory-linked diseases. However, aside from the onset of severe side-effects, chronic GC therapy often leads to the ligand-mediated downregulation of the GRα which, in turn, leads to a decrease in GC sensitivity, and effectively, the development of acquired GC resistance. Although the ligand-mediated downregulation of GRα is well documented, the precise factors which influence this process are not well understood and, thus, the development of an acquired GC resistance presents an ever-increasing challenge to the pharmaceutical industry. Recently, however, studies have correlated the dimerization status of the GRα with its ligand-mediated downregulation. Therefore, the current review will be discussing the major role-players in the homologous downregulation of the GRα pool, with a specific focus on previously reported GC-mediated reductions in GRα mRNA and protein levels, the molecular mechanisms through which the GRα functional pool is maintained and the possible impact of receptor conformation on GC-mediated GRα downregulation. |
| first_indexed | 2024-03-10T06:39:58Z |
| format | Article |
| id | doaj.art-e44ab430fb31418aa939be0bc355f008 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:58Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e44ab430fb31418aa939be0bc355f0082023-11-22T17:45:08ZengMDPI AGCells2073-44092021-09-011010252910.3390/cells10102529Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old ProblemLee-Maine L. Spies0Nicolette J. D. Verhoog1Ann Louw2Department of Biochemistry, Stellenbosch University, Van de Byl Street, Stellenbosch 7200, South AfricaDepartment of Biochemistry, Stellenbosch University, Van de Byl Street, Stellenbosch 7200, South AfricaDepartment of Biochemistry, Stellenbosch University, Van de Byl Street, Stellenbosch 7200, South AfricaFor over 70 years, the unique anti-inflammatory properties of glucocorticoids (GCs), which mediate their effects via the ligand-activated transcription factor, the glucocorticoid receptor alpha (GRα), have allowed for the use of these steroid hormones in the treatment of various autoimmune and inflammatory-linked diseases. However, aside from the onset of severe side-effects, chronic GC therapy often leads to the ligand-mediated downregulation of the GRα which, in turn, leads to a decrease in GC sensitivity, and effectively, the development of acquired GC resistance. Although the ligand-mediated downregulation of GRα is well documented, the precise factors which influence this process are not well understood and, thus, the development of an acquired GC resistance presents an ever-increasing challenge to the pharmaceutical industry. Recently, however, studies have correlated the dimerization status of the GRα with its ligand-mediated downregulation. Therefore, the current review will be discussing the major role-players in the homologous downregulation of the GRα pool, with a specific focus on previously reported GC-mediated reductions in GRα mRNA and protein levels, the molecular mechanisms through which the GRα functional pool is maintained and the possible impact of receptor conformation on GC-mediated GRα downregulation.https://www.mdpi.com/2073-4409/10/10/2529glucocorticoid receptor alphaglucocorticoidsglucocorticoid receptor dimerizationacquired glucocorticoid resistanceubiquitin-proteasome system |
| spellingShingle | Lee-Maine L. Spies Nicolette J. D. Verhoog Ann Louw Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem Cells glucocorticoid receptor alpha glucocorticoids glucocorticoid receptor dimerization acquired glucocorticoid resistance ubiquitin-proteasome system |
| title | Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
| title_full | Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
| title_fullStr | Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
| title_full_unstemmed | Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
| title_short | Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
| title_sort | acquired glucocorticoid resistance due to homologous glucocorticoid receptor downregulation a modern look at an age old problem |
| topic | glucocorticoid receptor alpha glucocorticoids glucocorticoid receptor dimerization acquired glucocorticoid resistance ubiquitin-proteasome system |
| url | https://www.mdpi.com/2073-4409/10/10/2529 |
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