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Carlos Alberto Longui - One of the best experts on this subject based on the ideXlab platform.
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Tissue-specific adaptive levels of Glucocorticoid Receptor Alpha mRNA and their relationship with insulin resistance.
Genetics and molecular research : GMR, 2012Co-Authors: R. B. Castro, Carlos Alberto Longui, Murilo Rezende Melo, C.d.c. Faria, T.s. Silva, F. Richeti, M.n. Rocha, W.l. Pereira, E.g. Chamlian, L.a. RivettiAbstract:Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified Glucocorticoid Receptor Alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11β-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11β-HSD1 mRNA concentration. We also observed significantly reduced 11β-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11β-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRαmRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.
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Quantitation of Glucocorticoid Receptor Alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients
Genetics and molecular research : GMR, 2010Co-Authors: L. O. Cavalcante, Murilo Rezende Melo, R. B. Castro, V. G. Dinis, B. D. B. Souza, Carlos Alberto LonguiAbstract:We measured NF-κB, IKK, c-Fos, and GRα mRNA expression and in vivo Glucocorticoid sensitivity in patients with rheumatoid arthritis. A very low dose intravenous dexamethasone suppression test and real-time PCR quantitation of mRNA of these genes were performed on blood samples from 21 rheumatoid arthritis patients who were not on Glucocorticoids during the previous four months and on blood samples from 20 healthy individuals. Mean rheumatoid arthritis duration was 8.8 years, and mean disease activity, as assessed by Disease Activity Score 28 (DAS28), was 4.45. Basal cortisol and the percentage of cortisol reduction after the very low dose intravenous dexamethasone suppression test, as well as NF-κB, IKK, c-Fos, and GRα mRNA expression, were similar among groups. We did not observe significant correlations between Glucocorticoid in vivo sensitivity and DAS28. There was a positive correlation between
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Simultaneous evaluation of in vivo Glucocorticoid sensitivity and expression of Glucocorticoid Receptor Alpha-isoform in rheumatoid arthritis patients
Arquivos brasileiros de endocrinologia e metabologia, 2009Co-Authors: Jayme F. Cobra, Carlos Alberto Longui, Murilo Rezende Melo, Claudia D. C. Faria, Osmar MonteAbstract:OBJECTIVES: To analyze Glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with Glucocorticoid Receptor Alpha-isoform (GRα) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity.
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Real-time PCR quantitation of Glucocorticoid Receptor Alpha isoform
BMC molecular biology, 2004Co-Authors: Murilo Rezende Melo, Claudia D. C. Faria, Keli Cardoso De Melo, Nancy Amaral Rebouças, Carlos Alberto LonguiAbstract:Background: The expression of Glucocorticoid-Receptor (GR) seems to be a key mechanism in the regulation of Glucocorticoid (GC) sensitivity and is potentially involved in cases of GC resistance or hypersensitivity. The aim of this study is to describe a method for quantitation of GR Alpha isoform (GRα) expression using real-time PCR (qrt-PCR) with analytical capabilities to monitor patients, offering standard-curve reproducibility as well as intra- and inter-assay precision. Results: Standard-curves were constructed by employing standardized Jurkat cell culture procedures, both for GRα and BCR (breakpoint cluster region), as a normalizing gene. We evaluated standard-curves using five different sets of cell culture passages, RNA extraction, reverse transcription, and qrt-PCR quantification. Intra-assay precision was evaluated using 12 replicates of each gene, for 2 patients, in a single experiment. Inter-assay precision was evaluated on 8 experiments, using duplicate tests of each gene for two patients. Standard-curves were reproducible, with CV (coefficient of variation) of less than 11%, and Pearson correlation coefficients above 0,990 for most comparisons. Intra-assay and inter-assay were 2% and 7%, respectively. Conclusion: This is the first method for quantitation of GRα expression with technical characteristics that permit patient monitoring, in a fast, simple and robust way.
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low Glucocorticoid Receptor Alpha beta ratio in t cell lymphoblastic leukemia
Hormone and Metabolic Research, 2000Co-Authors: Carlos Alberto Longui, Alessandra Vottero, Peter C. Adamson, Diane E. Cole, Tomoshige Kino, O Monte, George P. ChrousosAbstract:Glucocorticoid therapy is pivotal in the treatment of acute lymphoblastic leukemia (ALL); it reduces cell proliferation, promotes cell cycle arrest, and induces cell death by apoptosis. The sensitivity of leukemic cells to Glucocorticoids was previously related to the cell concentration of 3[H]dexamethasone-binding sites. The latter represents the classic Glucocorticoid Receptor (GR) isoform Alpha that binds ligand and modulates the transcription rates of Glucocorticoid-responsive genes. In ALL, lymphoblasts of T-lineage are less sensitive to Glucocorticoids than cells of the B-lineage. The alternatively spliced GR isoform (GRP), which exerts a dominant negative effect on GRAlpha-mediated transcriptional activity, has been proposed as a possible mediator of Glucocorticoid resistance. In this study, we determined the amount of GRAlpha and GRbeta in mononuclear cells from 13 newly diagnosed and untreated children with ALL and 9 controls by quantitative Western analysis. Generally, leukemic patients expressed 6 times less GRAlpha (ALL= 0.54 +/- 1.1; controls = 3.1 +/- 0.9; p < 0.01) than controls, but the same amount of GRbeta (ALL=3.62 +/- 3.3; controls = 3.6 +/- 3.4). ALL patients with T-cell disease had a much lower GRAlpha (0.09 +/- 0.1; p < 0.01) but a similar or slightly higher GRbeta (5.98 +/- 3.9; p = 0.1) expression than controls, with a GRAlpha/GRbeta ratio 15 times smaller than controls. Mononuclear leukocytes of T-cell lineage expressed significantly lower GRAlpha (p = 0.04) and higher GRbeta (p < 0.01) than cells of the pre-B immunophenotype, with a 10 times smaller ratio. We conclude that the combination of low GRAlpha and normal-to-high GRbeta expression in leukemic lymphoblasts might represent one of the mechanisms responsible for their reduced Glucocorticoid sensitivity; this is more pronounced in T-lineage cells.
Ioannis Ilias - One of the best experts on this subject based on the ideXlab platform.
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longitudinal evaluation of Glucocorticoid Receptor Alpha beta expression and signalling adrenocortical function and cytokines in critically ill steroid free patients
Molecular and Cellular Endocrinology, 2020Co-Authors: Alice G. Vassiliou, Ioannis Ilias, Georgios Stamogiannos, Edison Jahaj, Efi Botoula, Georgios Floros, Dimitra Vassiliadi, Stylianos Tsagarakis, Marinella Tzanela, Stylianos E. OrfanosAbstract: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.
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Longitudinal evaluation of Glucocorticoid Receptor Alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients.
Molecular and cellular endocrinology, 2019Co-Authors: Alice G. Vassiliou, Ioannis Ilias, Georgios Stamogiannos, Edison Jahaj, Efi Botoula, Georgios Floros, Dimitra Vassiliadi, Stylianos Tsagarakis, Marinella Tzanela, Stylianos E. OrfanosAbstract: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.
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L -Carnitine, Immunomodulation, and Human Immunodeficiency Virus (HIV)-related Disorders
Monatshefte für Chemie - Chemical Monthly, 2005Co-Authors: Salvatore Alesci, Mariana Gerschenson, Ioannis IliasAbstract:The use of pharmacologic doses of the conditionally-essential nutrient L-carnitine (LC) has been associated with positive effects on the immune system. We have recently suggested that this property of LC could be mediated through activation of the Glucocorticoid Receptor Alpha. Human immunodeficiency virus (HIV)-infected individuals, especially those on antiretroviral therapy, may become LC-deficient. This evidence, together with the immunomodulatory properties of LC, its known major role in lipid and energy metabolisms, and its proposed antiapoptotic and neuroprotective actions, have encouraged the use of LC supplementation as a potential treatment for HIV-related disorders, such as lipodystrophy and peripheral neuropathy. Preliminary results, mostly from small-scale uncontrolled studies are conflicting, whilst larger controlled trials are warranted.
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l carnitine is a modulator of the Glucocorticoid Receptor Alpha
Annals of the New York Academy of Sciences, 2004Co-Authors: Salvatore Alesci, Tomoshige Kino, Massimo U. De Martino, Ioannis IliasAbstract:L-Carnitine (LC) is a nutrient with an essential role in cellular energy production. At high doses, LC can mimic some of the biological activities of Glucocorticoids, particularly immunomodulation. To explore the molecular bases of this property, we tested the influence of LC on Glucocorticoid Receptor-a (GRAlpha) functions. LC reduced the binding capacity of GRAlpha, induced its nuclear translocation, and stimulated its transcriptional activity. Moreover, LC suppressed TNFAlpha and IL-12 release from human monocytes in Glucocorticoid-like fashion. We conclude that pharmacologic doses of LC can activate GRAlpha and, via this mechanism, regulate Glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of Glucocorticoids.
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l‐Carnitine Is a Modulator of the Glucocorticoid Receptor Alpha
Annals of the New York Academy of Sciences, 2004Co-Authors: Salvatore Alesci, Tomoshige Kino, Massimo U. De Martino, Ioannis IliasAbstract:L-Carnitine (LC) is a nutrient with an essential role in cellular energy production. At high doses, LC can mimic some of the biological activities of Glucocorticoids, particularly immunomodulation. To explore the molecular bases of this property, we tested the influence of LC on Glucocorticoid Receptor-a (GRAlpha) functions. LC reduced the binding capacity of GRAlpha, induced its nuclear translocation, and stimulated its transcriptional activity. Moreover, LC suppressed TNFAlpha and IL-12 release from human monocytes in Glucocorticoid-like fashion. We conclude that pharmacologic doses of LC can activate GRAlpha and, via this mechanism, regulate Glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of Glucocorticoids.
Murilo Rezende Melo - One of the best experts on this subject based on the ideXlab platform.
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Tissue-specific adaptive levels of Glucocorticoid Receptor Alpha mRNA and their relationship with insulin resistance.
Genetics and molecular research : GMR, 2012Co-Authors: R. B. Castro, Carlos Alberto Longui, Murilo Rezende Melo, C.d.c. Faria, T.s. Silva, F. Richeti, M.n. Rocha, W.l. Pereira, E.g. Chamlian, L.a. RivettiAbstract:Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified Glucocorticoid Receptor Alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11β-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11β-HSD1 mRNA concentration. We also observed significantly reduced 11β-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11β-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRαmRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.
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Quantitation of Glucocorticoid Receptor Alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients
Genetics and molecular research : GMR, 2010Co-Authors: L. O. Cavalcante, Murilo Rezende Melo, R. B. Castro, V. G. Dinis, B. D. B. Souza, Carlos Alberto LonguiAbstract:We measured NF-κB, IKK, c-Fos, and GRα mRNA expression and in vivo Glucocorticoid sensitivity in patients with rheumatoid arthritis. A very low dose intravenous dexamethasone suppression test and real-time PCR quantitation of mRNA of these genes were performed on blood samples from 21 rheumatoid arthritis patients who were not on Glucocorticoids during the previous four months and on blood samples from 20 healthy individuals. Mean rheumatoid arthritis duration was 8.8 years, and mean disease activity, as assessed by Disease Activity Score 28 (DAS28), was 4.45. Basal cortisol and the percentage of cortisol reduction after the very low dose intravenous dexamethasone suppression test, as well as NF-κB, IKK, c-Fos, and GRα mRNA expression, were similar among groups. We did not observe significant correlations between Glucocorticoid in vivo sensitivity and DAS28. There was a positive correlation between
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Simultaneous evaluation of in vivo Glucocorticoid sensitivity and expression of Glucocorticoid Receptor Alpha-isoform in rheumatoid arthritis patients
Arquivos brasileiros de endocrinologia e metabologia, 2009Co-Authors: Jayme F. Cobra, Carlos Alberto Longui, Murilo Rezende Melo, Claudia D. C. Faria, Osmar MonteAbstract:OBJECTIVES: To analyze Glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with Glucocorticoid Receptor Alpha-isoform (GRα) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity.
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Real-time PCR quantitation of Glucocorticoid Receptor Alpha isoform
BMC molecular biology, 2004Co-Authors: Murilo Rezende Melo, Claudia D. C. Faria, Keli Cardoso De Melo, Nancy Amaral Rebouças, Carlos Alberto LonguiAbstract:Background: The expression of Glucocorticoid-Receptor (GR) seems to be a key mechanism in the regulation of Glucocorticoid (GC) sensitivity and is potentially involved in cases of GC resistance or hypersensitivity. The aim of this study is to describe a method for quantitation of GR Alpha isoform (GRα) expression using real-time PCR (qrt-PCR) with analytical capabilities to monitor patients, offering standard-curve reproducibility as well as intra- and inter-assay precision. Results: Standard-curves were constructed by employing standardized Jurkat cell culture procedures, both for GRα and BCR (breakpoint cluster region), as a normalizing gene. We evaluated standard-curves using five different sets of cell culture passages, RNA extraction, reverse transcription, and qrt-PCR quantification. Intra-assay precision was evaluated using 12 replicates of each gene, for 2 patients, in a single experiment. Inter-assay precision was evaluated on 8 experiments, using duplicate tests of each gene for two patients. Standard-curves were reproducible, with CV (coefficient of variation) of less than 11%, and Pearson correlation coefficients above 0,990 for most comparisons. Intra-assay and inter-assay were 2% and 7%, respectively. Conclusion: This is the first method for quantitation of GRα expression with technical characteristics that permit patient monitoring, in a fast, simple and robust way.
H A Drexhage - One of the best experts on this subject based on the ideXlab platform.
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inflammatory activation is associated with a reduced Glucocorticoid Receptor Alpha beta expression ratio in monocytes of inpatients with melancholic major depressive disorder
Translational Psychiatry, 2014Co-Authors: L A Carvalho, V Bergink, L Sumaski, J Wijkhuijs, W J Hoogendijk, T K Birkenhager, H A DrexhageAbstract:In this study, we used new technology to investigate whether a coherent pattern of enhanced expression of inflammatory and other immune activation genes in circulating monocytes is found in patients with major depression. Since a high inflammatory state of monocytes might be related to Glucocorticoid resistance, we also included the genes for the two isoforms of the Glucocorticoid Receptor. For this study, we aimed at finding a similar coherent pattern of inflammatory and immune activation genes in monocytes of patients with MDD and recruited 47 medication-free melancholic MDD inpatients and 42 healthy controls. A quantitative-polymerase chain reaction (Q-PCR) monocyte gene expression analysis was performed using a panel of inflammatory-related genes previously identified as abnormally regulated in mood disorder patients. Selected serum cytokines/chemokines were assessed using a cytometric bead array. Depressive symptoms were analysed using Hamilton depression scores (HAMD). Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls, the latter including the gene for the active GRα in particular in those with a high HAMD score. The reduced GRα expression correlated strongly to the upregulation of the inflammatory genes in monocytes. Serum levels of IL6, IL8, CCL2 and VEGF were significantly increased in patients compared to controls. Our data show the deregulation of two interrelated homoeostatic systems, that is, the immune system and the Glucocorticoid system, co-occurring in major depression.
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Inflammatory activation is associated with a reduced Glucocorticoid Receptor Alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder
Translational Psychiatry, 2014Co-Authors: L A Carvalho, V Bergink, L Sumaski, J Wijkhuijs, W J Hoogendijk, T K Birkenhager, H A DrexhageAbstract:In this study, we used new technology to investigate whether a coherent pattern of enhanced expression of inflammatory and other immune activation genes in circulating monocytes is found in patients with major depression. Since a high inflammatory state of monocytes might be related to Glucocorticoid resistance, we also included the genes for the two isoforms of the Glucocorticoid Receptor. For this study, we aimed at finding a similar coherent pattern of inflammatory and immune activation genes in monocytes of patients with MDD and recruited 47 medication-free melancholic MDD inpatients and 42 healthy controls. A quantitative-polymerase chain reaction (Q-PCR) monocyte gene expression analysis was performed using a panel of inflammatory-related genes previously identified as abnormally regulated in mood disorder patients. Selected serum cytokines/chemokines were assessed using a cytometric bead array. Depressive symptoms were analysed using Hamilton depression scores (HAMD). Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls, the latter including the gene for the active GRα in particular in those with a high HAMD score. The reduced GRα expression correlated strongly to the upregulation of the inflammatory genes in monocytes. Serum levels of IL6, IL8, CCL2 and VEGF were significantly increased in patients compared to controls. Our data show the deregulation of two interrelated homoeostatic systems, that is, the immune system and the Glucocorticoid system, co-occurring in major depression.
Stylianos E. Orfanos - One of the best experts on this subject based on the ideXlab platform.
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longitudinal evaluation of Glucocorticoid Receptor Alpha beta expression and signalling adrenocortical function and cytokines in critically ill steroid free patients
Molecular and Cellular Endocrinology, 2020Co-Authors: Alice G. Vassiliou, Ioannis Ilias, Georgios Stamogiannos, Edison Jahaj, Efi Botoula, Georgios Floros, Dimitra Vassiliadi, Stylianos Tsagarakis, Marinella Tzanela, Stylianos E. OrfanosAbstract: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.
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Longitudinal evaluation of Glucocorticoid Receptor Alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients.
Molecular and cellular endocrinology, 2019Co-Authors: Alice G. Vassiliou, Ioannis Ilias, Georgios Stamogiannos, Edison Jahaj, Efi Botoula, Georgios Floros, Dimitra Vassiliadi, Stylianos Tsagarakis, Marinella Tzanela, Stylianos E. OrfanosAbstract: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.