Articles: glucocorticoid-receptors.
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Critical care medicine · Dec 2021
Observational StudyIncreased Glucocorticoid Receptor Alpha Expression and Signaling in Critically Ill Coronavirus Disease 2019 Patients.
Critical illness is characterized by increased serum cortisol concentrations and bioavailability resulting from the activation of the hypothalamic-pituitary-adrenal axis, which constitutes an essential part of the stress response. The actions of glucocorticoids are mediated by a ubiquitous intracellular receptor protein, the glucocorticoid receptor. So far, data on coronavirus disease 2019 and glucocorticoid receptor alpha expression are lacking. ⋯ ICU coronavirus disease 2019 patients showed upregulated glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper expression, along with cortisol levels, compared with ICU noncoronavirus disease 2019 patients. Thus, on ICU admission, critical coronavirus disease 2019 appears to be associated with hypercortisolemia, and increased synthesis of glucocorticoid receptor alpha and induced proteins.
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Randomized Controlled Trial
[The role and place of pathogenetic therapy with glucocorticosteroid hormones in the treatment of patients with novel coronavirus infection (COVID-19)].
In December 2019, in Wuhan (PRC), there was an outbreak of a new coronavirus infection (COVID-19) caused by coronavirus type 2 (SARS-CoV-2), which has a zoonotic origin. The World Health Organization announced the COVID-19 pandemic on March 11, 2020. In most cases, the disease is asymptomatic or mild. ⋯ However, until recently, there was no convincing data on the effectiveness of GCS in patients with COVID-19. Recently published results of a large randomized clinical trial (RECOVERY) showing the efficacy of GCS (dexamethasone) in the treatment of critically ill patients with COVID-19. At the same time, the feasibility and effectiveness of GCS in patients with COVID-19 outside critical conditions, the pathogenetic mechanisms that determine the effectiveness/ineffectiveness of these drugs and the validity of their use remain insufficiently studied.
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A potential cause of the variable response to injury and sepsis is the variability of a patient's human glucocorticoid receptor (hGR) profile. To identify hGR variants, blood samples were collected on admission and biweekly thereafter from hospitalized patients who sustained at least a 20% total body surface area burn injury. A hyperactive G1376T single-nucleotide polymorphism (SNP) isoform was identified. ⋯ With the combination of both RU486 and hydrocortisone, G459V activity was repressed, but greater than that of RU486 alone. Finally, when hGRα was cotransfected with G459V to simulate isoform interaction, the activity was closer to that of the hGRα profile than the G459V isoform. The unique activity of the G459V isoform shows that some variants of hGR have the potential to alter a person's response to stress and steroid treatment and may be a factor as to why mitigating the clinical response to sepsis and other stressors has been so elusive.
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The use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism. ⋯ By affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.