Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

“…Tissue resistance to glucocorticoids has been implicated in chronic inflammatory diseases such as chronic obstructive pulmonary disease, severe asthma, systemic lupus erythematosus, ulcerative colitis, and rheumatoid arthritis [76]. Glucocorticoid resistance is also recognized as a potential complication of critical illness, with most of the evidence originating from the sepsis and ARDS clinical and experimental literature [75][76][77][78][79][80][81]. Critical illness is associated with reduced GR-α density and transcription [7,25,82,83] and increased GR-β (dominant negative activity on GR-induced transcription) [80,83,84].…”

“…In addition there is decreased GR-α transcription in circulating cells and lymph node/spleen, in liver and kidney, and lung tissue [77]. Sepsis is also characterized by an increased expression of the GR isoform GR-β in circulating cells, resulting in an imbalance between GRα and GRβ [80,83].…”

MECHANISMS IN ENDOCRINOLOGY: New concepts to further unravel adrenal insufficiency during critical illness

“…However, plasma free cortisol assays are currently not readily available and normal ranges of plasma free cortisol during critical illness have not been defined. Additionally, increasing evidence from both animal and human experiments suggests that GR availability in different tissues, the GR affinity and translocation are regulated during critical illness (24,25,26,27,28,29). In septic patients, for example, the dominant negative b-isoform of the GR was induced from the onset of critical illness on, which downregulates glucocorticoid action (25).…”

α-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy

“…GR acts as a transcription factor for distinct target genes, regulating them through both direct DNA binding and proteineprotein interactions with other transcription factors [15]. It has been confirmed that GR is involved in the inflammatory response and plays an anti-inflammatory role [16,17]. GR was previously shown to translocate into the mitochondria and bind to the glucocorticoid response elements located in the mtDNA D-loop region [18,19], thereby exerting measurable effects on mitochondrial function [20].…”