Glucocorticoid and mineralocorticoid receptor expression in critical illness: A narrative review

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.