@article{3078385,
    title = "Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients",
    author = "Vassiliou, A.G. and Stamogiannos, G. and Jahaj, E. and Botoula, E. and Floros, G. and Vassiliadi, D.A. and Ilias, I. and Tsagarakis, S. and Tzanela, M. and Orfanos, S.E. and Kotanidou, A. and Dimopoulou, I.",
    journal = "Molecular and Cellular Endocrinology",
    year = "2020",
    volume = "501",
    publisher = "Elsevier Ireland Ltd",
    issn = "0303-7207",
    doi = "10.1016/j.mce.2019.110656",
    keywords = "corticotropin;  fk 506 binding protein;  FK506 binding protein 51;  glucocorticoid inducible gene leucine zipper;  glucocorticoid receptor alpha;  glucocorticoid receptor beta;  hydrocortisone;  interleukin 10;  interleukin 6;  interleukin 8;  leucine zipper protein;  messenger RNA;  tumor necrosis factor;  unclassified drug;  corticotropin;  cytokine;  glucocorticoid;  glucocorticoid receptor;  glucocorticoid receptor alpha;  glucocorticoid receptor beta;  hydrocortisone;  isoprotein;  steroid, adult;  Article;  clinical article;  controlled study;  critically ill patient;  demography;  enzyme linked immunosorbent assay;  female;  gene targeting;  hospital admission;  human;  hypothalamus hypophysis adrenal system;  intensive care unit;  male;  population research;  priority journal;  prospective study;  protein blood level;  protein expression;  protein RNA binding;  signal transduction;  adrenal cortex;  critical illness;  hypophysis adrenal system;  hypothalamus hypophysis system;  inborn error of metabolism;  longitudinal study;  metabolism;  middle aged;  physiology;  signal transduction, Adrenal Cortex;  Adrenocorticotropic Hormone;  Critical Illness;  Cytokines;  Female;  Glucocorticoids;  Humans;  Hydrocortisone;  Hypothalamo-Hypophyseal System;  Longitudinal Studies;  Male;  Metabolism, Inborn Errors;  Middle Aged;  Pituitary-Adrenal System;  Prospective Studies;  Protein Isoforms;  Receptors, Glucocorticoid;  Signal Transduction;  Steroids",
    abstract = "Purpose: Glucocorticoid actions are mediated by the glucocorticoid receptor (GCR) whose dysfunction leads to glucocorticoid tissue resistance. Our objective was to evaluate GCR-α and GCR-β expression and key steps in the GCR signalling cascade in critical illness. Methods: Expression of GCR and major GCR-target genes, cortisol, adrenocorticotropin (ACTH) and cytokines was measured in 42 patients on ICU admission and on days 4, 8, and 13. Twenty-five age- and sex-matched subjects were used as controls. Results: Acutely, mRNA expression of GCR-α was 10-fold and of GCR-β 3-fold the expression of controls, while during the sub-acute phase expression of both isoforms was lower compared to controls. Expression of FKBP5 and GILZ decreased significantly. Cortisol levels remained elevated and ACTH increased during the 13-day period. Conclusions: GCR expression and hypothalamic-pituitary-adrenal axis function undergo a biphasic response during critical illness. The dissociation between low GCR expression and high cortisol implies an abnormal stress response. © 2019 Elsevier B.V."
}