Alice G Vassiliou1, Georgios Stamogiannos2, Edison Jahaj2, Efi Botoula3, Georgios Floros2, Dimitra A Vassiliadi3, Ioannis Ilias4, Stylianos Tsagarakis3, Marinella Tzanela3, Stylianos E Orfanos5, Anastasia Kotanidou5, Ioanna Dimopoulou6. 1. 1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece. 2. 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece. 3. Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece. 4. Endocrine Unit, Elena Venizelou Hospital, Athens, Greece. 5. 1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece; 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece. 6. 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece. Electronic address: idimo@otenet.gr.
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.
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.
Authors: Arno Téblick; Lisa Van Dyck; Nathalie Van Aerde; Sarah Van der Perre; Lies Pauwels; Inge Derese; Yves Debaveye; Pieter J Wouters; Ilse Vanhorebeek; Lies Langouche; Greet Van den Berghe Journal: EBioMedicine Date: 2022-05-15 Impact factor: 11.205