Lessons from Glucocorticoid Receptor Action in Bone: New Ways to Avoid Side Effects of Steroid Therapy

2012 ◽  
pp. 31-48 ◽  
Author(s):  
Alexander Rauch ◽  
Ulrike Baschant ◽  
Jan Tuckermann
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Steroid Therapy ◽  
Receptor Action

Regulation of glucocorticoid receptor action by ARID subunits of the SWI/SNF complex

2015 ◽  
Author(s):  
Felicity Ellen Russell ◽  
Becky L Conway-Campbell ◽  
Matthew Birnie ◽  
Simon Biddie ◽  
Stafford Lightman
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Action

scholarly journals Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Snehal S. Patel ◽  
Azza A. K. El-Sheikh ◽  
Jignasa K. Savjani ◽  
Anroop B. Nair ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Withaferin A ◽  
Boswellic Acid ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Necrosis Factor

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

scholarly journals Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2529
Author(s):  
Lee-Maine L. Spies ◽  
Nicolette J. D. Verhoog ◽  
Ann Louw
Keyword(s):  
Transcription Factor ◽  
Side Effects ◽  
Pharmaceutical Industry ◽  
Glucocorticoid Receptor ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Protein Levels ◽  
Current Review ◽  
Role Players ◽  
Receptor Conformation

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.

Side Effects of Long Term Steroid Therapy in Chronic Lung Disease

Respiration ◽  
1970 ◽  
Vol 27 (1) ◽  
pp. 280-281
Author(s):  
K.F. Kerrebijn
Keyword(s):  
Side Effects ◽  
Lung Disease ◽  
Steroid Therapy ◽  
Chronic Lung Disease

P0430EFFECT OF CORTICOSTEROIDS THERAPY FOR PATIENTS OF IGA NEPHROPATHY WITH CRESCENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mengjun Liang ◽  
Aihua Li ◽  
Zongpei Jiang
Keyword(s):  
Renal Function ◽  
Side Effects ◽  
Iga Nephropathy ◽  
Steroid Therapy ◽  
Oral Prednisone ◽  
Pulse Therapy ◽  
The Other ◽  
Intravenous Methylprednisolone ◽  
Steroid Pulse ◽  
Renal Function Deterioration

Abstract Background and Aims Patients with IgA nephropathy (IgAN) presented proteinuria≥1g/d and eGFR≥50ml/min/1.73m2 after supportive treatment had been advised 6-month course of corticosteroids therapy. Update of Oxford classification of IgAN had recommended crescents be added to the MEST score for they were predictive of outcome. Whether we should take some more positive therapy for crescents? Method We conducted a single-center, retrospective cohort study enrolling 46 patients from 2017.01 to 2018.06, diagnosed with IgAN by renal biopsy. Eligible patients had proteinuria of 0.5∼3.5g/d, eGFR≥30ml/min/1.73m2 and crescent proportion <50%. Patients were divided into two groups, one for classical steroid treatment (intravenous methylprednisolone 0.25g/d for 3 days at the beginning of months 1, 3 and 5, plus oral prednisone 0.5 mg/kg/d for 6 months, called 1-3-5 Group) and the other assigned an optimized steroid therapy (intravenous methylprednisolone 0.25g/d for 3 days at the beginning of months 1, 2 and 3, plus oral prednisone 0.5 mg/kg/d for 6 months, called 1-2-3 Group). The primary endpoint was remission of proteinuria, secondary endpoint was deterioration in renal function. Results There were 23 patients in each group and no significant differences in age, gentle, baseline proteinuria and eGFR between the two groups, except for the proportion of crescents (for Oxford C1 and C2: 52.5% and 13% in 1-3-5 Group vs. 95.7% and 4.3% in 1-2-3 Group respectively, p=0.001). After 6 months therapy, proteinuria in 1-3-5 Group was 0.5(0.2,0.8)g/d (vs. 1.2(0.8,2.6)g/d at baseline, p <0.001) and that in 1-2-3 Group was 0.3(0.2,0.6)g/d (vs. 1.5(0.7,2.6)g/d at baseline, p <0.001). 78.3% of patients in 1-3-5 Group had got remission of proteinuria, while 95.7% in 1-2-3 Group (p=0.187). The 6th month eGFR in 1-3-5 Group was 80.7(59.8,116.2)ml/min/1.73m2 (vs. 77.5(54.8,104.6)ml/min/1.73m2 at baseline, p=0.212), while that in 1-2-3 Group was 97.8(68.6,130.9)ml/min/1.73m2 (vs. 79.5(52.9,108.7)ml/min/1.73m2 at baseline, p=0.002). The slope of eGFR in 1-3-5 Group was 0.7(-1.7,3.3)ml/min/1.73m2/month, while that in 1-2-3 Group was 3(1.2,5.4)ml/min/1.73m2/month, p=0.027. For side effects, two patients in 1-2-3 Group had met bronchitis during the 2nd and 3rh therapy-month respectively; in 1-3-5 Group, one patient had got glaucoma during the 2nd therapy-month and the other had happened steroid-induced diabetes mellitus during the 3rd therapy-month. Conclusion Our preliminary results had indicated that optimized steroid therapy had equal effect on reducing proteinuria but more significant advantage to protect against renal function deterioration in IgAN with crescents. 1-2-3 month-steroid pulse therapy had not increase the morbidity of irreversible or severe side effects.

Psychiatric Side Effects of Steroid Therapy

1989 ◽  
Vol 30 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Pamela Kershner ◽  
Rebekah Wang-Cheng
Keyword(s):  
Side Effects ◽  
Steroid Therapy ◽  
Psychiatric Side Effects

Molecular dynamics of ultradian glucocorticoid receptor action

2012 ◽  
Vol 348 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Becky L. Conway-Campbell ◽  
John R. Pooley ◽  
Gordon L. Hager ◽  
Stafford L. Lightman
Keyword(s):  
Molecular Dynamics ◽  
Glucocorticoid Receptor ◽  
Receptor Action
Sign in / Sign up

Export Citation Format

Share Document