Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients.

Molecular and cellular endocrinology 2020 Feb 05

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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. 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. 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. 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. Copyright © 2019 Elsevier B.V. All rights reserved.

Citation

Alice G Vassiliou, Georgios Stamogiannos, Edison Jahaj, Efi Botoula, Georgios Floros, Dimitra A Vassiliadi, Ioannis Ilias, Stylianos Tsagarakis, Marinella Tzanela, Stylianos E Orfanos, Anastasia Kotanidou, Ioanna Dimopoulou. Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients. Molecular and cellular endocrinology. 2020 Feb 05;501:110656