Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients. (5th February 2020)

• Record Type: Journal Article
• Authors: Vassiliou, Alice G.; Stamogiannos, Georgios; Jahaj, Edison; Botoula, Efi; Floros, Georgios; Vassiliadi, Dimitra A.; Ilias, Ioannis; Tsagarakis, Stylianos; Tzanela, Marinella; Orfanos, Stylianos E.; Kotanidou, Anastasia; Dimopoulou, Ioanna
• Is Part Of: Molecular and cellular endocrinology. Volume 501(2020)
• Publication Date: 2020-02-05
• Subjects: Critical illness -- Stress response -- Cortisol -- Glucocorticoid receptors -- Interleukins; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.110656
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: GCR expression and HPA axis function undergo a biphasic response. Acutely, GCR expression is increased. No trans-activation or trans-repression of GCR-target genes occurs. Sub-acutely, dissociation between low GCR expression and high cortisol. Abnormal stress response.