Cargando…
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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533966/ https://www.ncbi.nlm.nih.gov/pubmed/34685511 http://dx.doi.org/10.3390/cells10102529 |
_version_ | 1784587441281171456 |
---|---|
author | Spies, Lee-Maine L. Verhoog, Nicolette J. D. Louw, Ann |
author_facet | Spies, Lee-Maine L. Verhoog, Nicolette J. D. Louw, Ann |
author_sort | Spies, Lee-Maine L. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8533966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85339662021-10-23 Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem Spies, Lee-Maine L. Verhoog, Nicolette J. D. Louw, Ann Cells Review 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. MDPI 2021-09-24 /pmc/articles/PMC8533966/ /pubmed/34685511 http://dx.doi.org/10.3390/cells10102529 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Spies, Lee-Maine L. Verhoog, Nicolette J. D. Louw, Ann Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem |
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 | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533966/ https://www.ncbi.nlm.nih.gov/pubmed/34685511 http://dx.doi.org/10.3390/cells10102529 |
work_keys_str_mv | AT spiesleemainel acquiredglucocorticoidresistanceduetohomologousglucocorticoidreceptordownregulationamodernlookatanageoldproblem AT verhoognicolettejd acquiredglucocorticoidresistanceduetohomologousglucocorticoidreceptordownregulationamodernlookatanageoldproblem AT louwann acquiredglucocorticoidresistanceduetohomologousglucocorticoidreceptordownregulationamodernlookatanageoldproblem |