Τίτλος:
Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Vassiliou, A.G.
Stamogiannos, G.
Jahaj, E.
Botoula, E.
Floros, G.
Vassiliadi, D.A.
Ilias, I.
Tsagarakis, S.
Tzanela, M.
Orfanos, S.E.
Kotanidou, A.
Dimopoulou, I.
Περιοδικό:
Molecular and Cellular Endocrinology
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.mce.2019.110656
