Down-Regulation of the Mineralocorticoid Receptor (MR) and Up-Regulation of Hydroxysteroid 11-Beta Dehydrogenase Type 2 (HSD11B2) Isoenzyme in Critically Ill Patients.
| Title: | Down-Regulation of the Mineralocorticoid Receptor (MR) and Up-Regulation of Hydroxysteroid 11-Beta Dehydrogenase Type 2 (HSD11B2) Isoenzyme in Critically Ill Patients. |
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| Authors: | Vassiliou AG; 1 Department of Critical Care Medicine & Pulmonary Services, National & Kapodistrian University of Athens, 'Evangelismos' Hospital, Athens, Greece.; Vassiliadi DA; Department of Endocrinology, Diabetes and Metabolism, National Expertise Centre for Rare Endocrine Diseases, 'Evangelismos' Hospital, Athens, Greece.; Keskinidou C; 1 Department of Critical Care Medicine & Pulmonary Services, National & Kapodistrian University of Athens, 'Evangelismos' Hospital, Athens, Greece.; Jahaj E; 1 Department of Critical Care Medicine & Pulmonary Services, National & Kapodistrian University of Athens, 'Evangelismos' Hospital, Athens, Greece.; Botoula E; Department of Endocrinology, Diabetes and Metabolism, National Expertise Centre for Rare Endocrine Diseases, 'Evangelismos' Hospital, Athens, Greece.; Tsagarakis S; Department of Endocrinology, Diabetes and Metabolism, National Expertise Centre for Rare Endocrine Diseases, 'Evangelismos' Hospital, Athens, Greece.; Kotanidou A; 1 Department of Critical Care Medicine & Pulmonary Services, National & Kapodistrian University of Athens, 'Evangelismos' Hospital, Athens, Greece.; Dimopoulou I; 1 Department of Critical Care Medicine & Pulmonary Services, National & Kapodistrian University of Athens, 'Evangelismos' Hospital, Athens, Greece idimo@otenet.gr. |
| Source: | Clinical medicine & research [Clin Med Res] 2023 Mar; Vol. 21 (1), pp. 6-13. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Marshfield Clinic Country of Publication: United States NLM ID: 101175887 Publication Model: Print Cited Medium: Internet ISSN: 1554-6179 (Electronic) Linking ISSN: 15394182 NLM ISO Abbreviation: Clin Med Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Marshfield, WI : Marshfield Clinic, c2002- |
| MeSH Terms: | 11-beta-Hydroxysteroid Dehydrogenase Type 2*/genetics ; 11-beta-Hydroxysteroid Dehydrogenase Type 2*/metabolism ; Receptors, Mineralocorticoid*/genetics ; Receptors, Mineralocorticoid*/metabolism ; Aldosterone*; Hydrocortisone/metabolism ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Renin/genetics ; Renin/metabolism ; Humans ; Critical Illness ; Down-Regulation ; Hydroxysteroids ; Prospective Studies ; Up-Regulation |
| Abstract: | Objective: The mineralocorticoid receptor (MR) has two ligands, aldosterone and cortisol. Hydroxysteroid 11-beta dehydrogenase (HSD11B) isoenzymes regulate which ligand will bind to MR. In this study we aimed to evaluate the expression of the MR and the HSD11B isozymes in peripheral polymorphonuclear cells (PMNs) in critical illness for a 13-day period.Design: Prospective studySetting: One multi-disciplinary intensive care unit (ICU)Participants: Forty-two critically ill patientsMethods: Messenger RNA (mRNA) expression of MR, HSD11B1, and HSD11B2, aldosterone levels, and plasma renin activity (PRA) were measured in 42 patients on ICU admission and on days 4, 8, and 13. Twenty-five age and sex-matched healthy subjects were used as controls.Results: Compared to healthy controls, MR expression in critically ill patients was lower during the entire study period. HSD11B1 expression was also lower, while HSD11B2 expression was higher. In patients, PRA, aldosterone, the aldosterone:renin ratio, and cortisol remained unaltered during the study period.Conclusion: Our results suggest that, in our cohort of critically ill patients, local endogenous cortisol availability is diminished, pointing towards glucocorticoid resistance. Aldosterone probably occupies the MR, raising the possibility that PMNs might be useful to study to gain insights into MR functionality during pathological states.; (Copyright © 2023 Marshfield Clinic Health System.) |
| Competing Interests: | Disclosure: The authors have not reported any financial or personal conflicts of interest related to this research. |
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| Contributed Indexing: | Keywords: Aldosterone; Cortisol; Critical illness; Hydroxysteroid 11-beta dehydrogenase; Mineralocorticoid receptor; Neutrophils |
| Substance Nomenclature: | EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2); 4964P6T9RB (Aldosterone); EC 1.1.1.146 (HSD11B2 protein, human); WI4X0X7BPJ (Hydrocortisone); 0 (Hydroxysteroids); 0 (Isoenzymes); 0 (Receptors, Mineralocorticoid); EC 3.4.23.15 (Renin); 0 (NR3C2 protein, human) |
| Entry Date(s): | Date Created: 20230502 Date Completed: 20230519 Latest Revision: 20230519 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10153682 |
| DOI: | 10.3121/cmr.2023.1743 |
| PMID: | 37130784 |
| Database: | MEDLINE |
Journal Article