Decreased glucocorticoid receptor expression during critical illness

2019 ◽  
Vol 49 (4) ◽  
pp. e13073 ◽  
Author(s):  
Alice G. Vassiliou ◽  
Georgios Floros ◽  
Edison Jahaj ◽  
Georgios Stamogiannos ◽  
Sofianna Gennimata ◽  
...  
Keyword(s):  
Critical Illness ◽  
Glucocorticoid Receptor ◽  
Receptor Expression

scholarly journals Pituitary–Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19

2021 ◽  
Vol 22 (21) ◽  
pp. 11473
Author(s):  
Dimitra A. Vassiliadi ◽  
Alice G. Vassiliou ◽  
Ioannis Ilias ◽  
Stylianos Tsagarakis ◽  
Anastasia Kotanidou ◽  
...  
Keyword(s):  
Stress Response ◽  
Critical Illness ◽  
Glucocorticoid Receptor ◽  
Critically Ill ◽  
Hpa Axis ◽  
Systemic Inflammation ◽  
Critically Ill Patients ◽  
Tissue Damage ◽  
Receptor Expression ◽  
Metabolic Effects

The hypothalamus–pituitary–adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).

Vitamin D decreasesin vitroglucocorticoid sensitivity via down regulation of glucocorticoid receptor expression

2015 ◽  
Author(s):  
Narjes Nasiri Ansari ◽  
Eliana Spilioti ◽  
Vasiliki Kalotychou ◽  
Geena Dalagiorgou ◽  
Paraskevi Moutsatsou ◽  
...  
Keyword(s):  
Vitamin D ◽  
Glucocorticoid Receptor ◽  
Receptor Expression ◽  
Down Regulation

Reduced Glucocorticoid Receptor Protein Expression in Children with Critical Illness

2013 ◽  
Vol 79 (3) ◽  
pp. 169-178 ◽  
Author(s):  
Justin A. Indyk ◽  
Cristina Candido-Vitto ◽  
Irene M. Wolf ◽  
Shekhar Venkataraman ◽  
Ricardo Munoz ◽  
...  
Keyword(s):  
Critical Illness ◽  
Glucocorticoid Receptor ◽  
Protein Expression ◽  
Receptor Protein

Differential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines.

Endocrinology ◽  
1993 ◽  
Vol 133 (1) ◽  
pp. 248-256 ◽  
Author(s):  
R R Denton ◽  
L P Eisen ◽  
M S Elsasser ◽  
J M Harmon
Keyword(s):  
Glucocorticoid Receptor ◽  
B Cell ◽  
Cell Lines ◽  
Receptor Expression

Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis

1992 ◽  
Vol 12 (2) ◽  
pp. 589-597
Author(s):  
E S Dieken ◽  
R L Miesfeld
Keyword(s):  
Transcriptional Regulation ◽  
Glucocorticoid Receptor ◽  
Target Genes ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Transactivation Domain ◽  
Lymphocyte Apoptosis ◽  
Murine Cell Line ◽  
N Terminus ◽  
Simplex Virus

Genetic studies have suggested that transcriptional regulation of specific target genes (by either induction or repression) is the molecular basis of glucocorticoid-mediated lymphocyte apoptosis. To examine the role of transcriptional regulation more directly, we developed a complementation assay utilizing stable transfection of wild-type (wt) and mutant (nti) glucocorticoid receptor (GR) cDNA constructs into a GR-deficient S49 murine cell line (7r). Our data confirm that the level of functional GR is rate limiting for S49 apoptosis and moreover that the GR amino terminus (N terminus), which as been deleted from the nti GR, is absolutely required for complementation in this system. Surprisingly, we found that at physiological levels of receptor, expression of the nti GR in cells containing wt GR results in enhanced dexamethasone sensitivity rather than a dominant negative phenotype. One interpretation of these data is that DNA binding by wt-nti heterodimers may be functionally similar to that of wt-wt homodimers, indicating that GRE occupancy by at least one transactivation domain may be sufficient to induce the hormonal response. To determine whether acidic activating sequences such as those localized to the GR N terminus are important in the induction of lymphocyte apoptosis, we tested the activity of a chimeric receptor in which we replaced the entire GR N terminus with sequences from the herpes simplex virus VP16 protein. Our results demonstrate that 7r cells expressing VP-GR fusions are indeed steroid sensitive, strongly supporting the idea that S49 apoptosis is dependent on transcriptional regulation of specific genes which respond to acidic activating domains, implying that induction, rather than repression, may be the critical initiating event.

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