Vassiliou Alice G, Athanasiou Nikolaos, Vassiliadi Dimitra A, Jahaj Edison, Keskinidou Chrysi, Kotanidou Anastasia, Dimopoulou Ioanna
1 Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National & Kapodistrian University of Athens, "Evangelismos" Hospital, Athens 10676, Greece.
Department of Endocrinology, Diabetes and Metabolism, "Evangelismos" Hospital, Athens 10676, Greece.
World J Crit Care Med. 2021 Jul 9;10(4):102-111. doi: 10.5492/wjccm.v10.i4.102.
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.
糖皮质激素受体（GCR）和盐皮质激素受体（MR）是激素依赖性转录因子类固醇受体超家族的成员。这些受体在结构和功能上相关。它们定位于细胞质中，在配体结合后转位进入细胞核。GCR和MR可在同一细胞中共表达，据信GCR和MR表达的平衡对于体内稳态至关重要，并在正常适应中起关键作用。在危重病中，下丘脑 - 垂体 - 肾上腺轴被激活，因此血清皮质醇浓度升高。然而，许多患者的皮质醇水平相对于疾病严重程度而言较低。糖皮质激素（GC）的作用由GCR促进，其功能障碍导致GC组织抵抗。MR在这个家族中是独特的，因为它既能结合醛固酮又能结合皮质醇。内源性GC在控制危重病中的炎症反应中起关键作用。由于1型和2型两种11β-羟基类固醇脱氢酶同工酶的作用，细胞内GC浓度可能与血液水平有很大差异。11β-羟基类固醇脱氢酶使内源性活性皮质醇和本质上无活性的可的松相互转化。这两种同工酶的表达程度有可能显著影响细胞和组织内局部GC的可用性。在这篇综述中，我们将探讨旨在阐明MR和GCR表达在危重病中所见炎症反应中的作用的临床研究。
