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World J Crit Care Med. Jul 9, 2021; 10(4): 102-111
Published online Jul 9, 2021. doi: 10.5492/wjccm.v10.i4.102
Glucocorticoid and mineralocorticoid receptor expression in critical illness: A narrative review
Alice G Vassiliou, Nikolaos Athanasiou, Dimitra A Vassiliadi, Edison Jahaj, Chrysi Keskinidou, Anastasia Kotanidou, Ioanna Dimopoulou
Alice G Vassiliou, Nikolaos Athanasiou, Edison Jahaj, Chrysi Keskinidou, Anastasia Kotanidou, Ioanna Dimopoulou, 1st Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National & Kapodistrian University of Athens, “Evangelismos” Hospital, Athens 10676, Greece
Dimitra A Vassiliadi, Department of Endocrinology, Diabetes and Metabolism, “Evangelismos” Hospital, Athens 10676, Greece
Author contributions: Vassiliou AG, Athanasiou N, Vassiliadi DA, Jahaj E, Keskinidou C, Kotanidou A and Dimopoulou I drafted the manuscript; Vassiliou AG, Vassiliadi DA, Kotanidou A and Dimopoulou I performed the final editing.
Conflict-of-interest statement: There is no conflict of interest associated with the senior author or any other co-author who contributed his/her efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ioanna Dimopoulou, MD, PhD, Professor, 1st Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National & Kapodistrian University of Athens, “Evangelismos” Hospital, Ipsilantou 45-47, Athens 10676, Greece. idimo@otenet.gr
Received: January 20, 2021
Peer-review started: January 20, 2021
First decision: February 15, 2021
Revised: February 18, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: July 9, 2021
Processing time: 167 Days and 13.1 Hours
Abstract

The glucocorticoid receptor (GCR) and the mineralocorticoid receptor (MR) are members of the steroid receptor superfamily of hormone-dependent transcription factors. The receptors are structurally and functionally related. They are localized in the cytosol and translocate into the nucleus after ligand binding. GCRs and MRs can be co-expressed within the same cell, and it is believed that the balance in GCR and MR expression is crucial for homeostasis and plays a key role in normal adaptation. In critical illness, the hypothalamic-pituitary-adrenal axis is activated, and as a consequence, serum cortisol concentrations are high. However, a number of patients exhibit relatively low cortisol levels for the degree of illness severity. Glucocorticoid (GC) actions are facilitated by GCR, whose dysfunction leads to GC tissue resistance. The MR is unique in this family in that it binds to both aldosterone and cortisol. Endogenous GCs play a critical role in controlling inflammatory responses in critical illness. Intracellular GC concentrations can differ greatly from blood levels due to the action of the two 11β-hydroxysteroid dehydrogenase isozymes, type 1 and type 2. 11β-hydroxysteroid dehydrogenases interconvert endogenous active cortisol and intrinsically inert cortisone. The degree of expression of the two isozymes has the potential to dramatically influence local GC availability within cells and tissues. In this review, we will explore the clinical studies that aimed to elucidate the role of MR and GCR expression in the inflammatory response seen in critical illness.

Keywords: Mineralocorticoid receptor; Glucocorticoid receptor, Critical illness; 11beta-hydroxysteroid dehydrogenase; Aldosterone; Cortisol

Core Tip: Endogenous glucocorticoids (GCs) play a critical role in controlling inflammatory responses in critical illness. Intracellular GC concentrations can differ greatly due to the action of the two 11β-hydroxysteroid dehydrogenase isozymes. The degree of expression of the two isozymes has the potential to dramatically influence local GC availability. The GC receptor and the mineralocorticoid receptor are members of the steroid receptor superfamily of hormone-dependent transcription factors. The study of the mineralocorticoid receptor and GC receptor expression and function in the inflammatory response seen in critical illness might aid in identifying the patients who will benefit from exogenous corticosteroid administration.