TY - JOUR
TI - Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients
AU - Vassiliou, A.G.
AU - Stamogiannos, G.
AU - Jahaj, E.
AU - Botoula, E.
AU - Floros, G.
AU - Vassiliadi, D.A.
AU - Ilias, I.
AU - Tsagarakis, S.
AU - Tzanela, M.
AU - Orfanos, S.E.
AU - Kotanidou, A.
AU - Dimopoulou, I.
JO - Molecular and Cellular Endocrinology
PY - 2020
VL - 501
TODO - null
SP - null
PB - Elsevier Ireland Ltd
SN - 0303-7207
TODO - 10.1016/j.mce.2019.110656
TODO - 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
TODO - 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.
ER -