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mineralocorticoid receptor

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https://www.readbyqxmd.com/read/28938454/11%C3%AE-hsd2-sumoylation-modulates-cortisol-induced-mineralocorticoid-receptor-nuclear-translocation-independently-of-effects-on-transactivation
#1
Rubén Jiménez-Canino, Fabián Lorenzo-Díaz, Alex Odermatt, Matthew A Bailey, Dawn E W Livingstone, Frederic Jaisser, Nicolette Farman, Diego Alvarez de la Rosa
The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has an essential role in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor (MR) by converting 11β-hydroxyglucocorticoids to inactive 11-ketosteroids. Congenital deficiency of 11β-HSD2 causes a form of salt-sensitive hypertension known as the syndrome of apparent mineralocorticoid excess. The disease phenotype, which ranges from mild to severe, correlates well with reduction in enzyme activity. Furthermore, polymorphisms in the 11β-HSD2 coding gene (HSD11B2) have been linked to high blood pressure and salt-sensitivity, major cardiovascular risk factors...
September 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28932959/the-role-and-regulation-of-the-11-beta-hydroxysteroid-dehydrogenase-enzyme-system-in-patients-with-inflammatory-bowel-disease
#2
M Hussey, G Holleran, S Smith, Mark Sherlock, D McNamara
INTRODUCTION: Glucocorticoids are known to modulate a number of immunological responses including counteracting inflammation. Within tissues expressing the glucocorticoid and mineralocorticoid receptors including the colon, glucocorticoid metabolism is regulated by the isoenzymes of 11ß-hydroxysteroid dehydrogenase (11β-HSD). 11β-HSD1 acts as an oxidoreductase converting inactive cortisone into active cortisol, while 11β-HSD2 acts as a dehydrogenase converting active cortisol to inactive cortisone...
September 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28931177/effects-of-aldosterone-on-chemerin-expression-and-secretion-in-3t3-l1-adipocytes
#3
Junhua Ma, Fei Sun, Jingnan Wang, He Jiang, Jiancan Lu, Xing Wang, Jichen Zhang, Chao Shi, Wen You, Xiangqi Li, Hongling Zhu, Mingjun Gu
Aldosterone plays a pivotal role in the pathogenesis of metabolic syndrome and cardiovascular disease; however, the underlying mechanisms have not been clarified. Chemerin has been characterized as an adipokine with crucial roles in obesity-associated disorders and cardiovascular homeostasis. The aim of the present study was to investigate the direct effects of aldosterone on chemerin expression and secretion in 3T3-L1 adipocytes and to identify the potential signalling pathways involved. Chemerin mRNA levels were measured using real-time PCR, whereas the levels of secreted chemerin in the culture media were determined using ELISA...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28930614/inter-species-functional-interactome-of-nuclear-steroid-receptors-r1
#4
Styliani A Geronikolou, Athanasia Pavlopoulou, Christina Kanaka-Gantenbein, George Chrousos
Steroids exert their actions by binding to the glucocorticoid, mineralocorticoid, androgen, estrogen and progesterone classes of receptors. Despite an exponential increase in our knowledge of steroid receptors, their interactions with other molecules, subcellular location and functions still need further elucidation. To unravel the mechanism(s) of action of the steroid hormones, as well as the function of their cognate nuclear receptors, an interaction network was created (henceforth referred to as "R1 Interactome")- illustrating that robust interactions have been preserved in rodents, frog, zebra fish and drosophila...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28926607/the-novel-mineralocorticoid-receptor-antagonist-finerenone-attenuates-neointima-formation-after-vascular-injury
#5
Jochen Dutzmann, Robert-Jonathan Musmann, Marco Haertlé, Jan-Marcus Daniel, Kristina Sonnenschein, Andreas Schäfer, Peter Kolkhof, Johann Bauersachs, Daniel G Sedding
BACKGROUND: The novel nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone holds promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidney disease. However, its effects on vascular function remain elusive. PURPOSE: The aim of this study was to determine the functional effect of selective MR antagonism by finerenone in vascular cells in vitro and the effect on vascular remodeling following acute vascular injury in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28921054/association-of-mineralocorticoid-receptor-antagonist-use-and-in-hospital-outcomes-in-patients-with-acute-heart-failure
#6
Vasiliki Bistola, Panagiotis Simitsis, Dimitrios Farmakis, Ignatios Ikonomidis, Georgios Bakosis, Filippos Triposkiadis, Erifili Hatziagelaki, John Lekakis, Alexandre Mebazaa, John Parissis
Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects...
September 18, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28920862/enhanced-endothelium-epithelial-sodium-channel-signaling-prompts-left-ventricular-diastolic-dysfunction-in-obese-female-mice
#7
Guanghong Jia, Javad Habibi, Annayya R Aroor, Michael A Hill, Vincent G DeMarco, Li E Lee, Lixin Ma, Brady J Barron, Adam Whaley-Connell, James R Sowers
OBJECTIVE: Enhanced activation of cell specific mineralocorticoid receptors (MRs) in obesity plays a key role in the development of cardiovascular disease including cardiac diastolic dysfunction as a critical prognosticator. Our previous investigations demonstrated that selective endothelium MR activation promotes a maladaptive inflammatory response and fibrosis in cardiovascular tissue in female mice fed a western diet (WD), and this was associated with expression and activation of the epithelial sodium channel on the surface of endothelial cells (EnNaC)...
September 8, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28918310/effect-of-eplerenone-on-markers-of-bone-turnover-in-patients-with-primary-hyperparathyroidism-the-randomized-placebo-controlled-epath-trial
#8
Nicolas Verheyen, Martin R Grübler, Andreas Meinitzer, Christian Trummer, Verena Schwetz, Karin Amrein, Hans P Dimai, Winfried März, Cristiana Catena, Dirk von Lewinski, Jakob Voelkl, Ioana Alesutan, Astrid Fahrleitner-Pammer, Helmut Brussee, Stefan Pilz, Andreas Tomaschitz
Mineralocorticoid receptor (MR) antagonism may affect bone turnover via direct and indirect pathways involving parathyroid hormone, but randomized controlled trials are lacking. In a pre-specified analysis of the "Eplerenone in primary hyperparathyroidism" placebo-controlled, randomized trial (ISRCTN 33941607), effects of eight weeks MR-blockade with eplerenone on bone turnover markers in 97 patients with primary hyperparathyroidism were tested. Mean age was 67.5±9.5years, and 76 (78.4%) were females. In analysis of covariance with adjustment for baseline values, eplerenone had no significant effect on isoform 5b of the tartrate-resistant acid phosphatase (TRAP), beta-crosslaps, N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin and bone-specific alkaline phosphatase...
September 14, 2017: Bone
https://www.readbyqxmd.com/read/28915330/impact-of-adrenal-steroids-on-regulation-of-adipose-tissue
#9
Marco Infante, Andrea Armani, Caterina Mammi, Andrea Fabbri, Massimiliano Caprio
Corticosteroids are secreted by the adrenal glands and control the functions of adipose tissue via the activation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). In turn, adipocytes release a large variety of adipokines into the bloodstream, regulating the function of several organs and tissues, including the adrenal glands, hereby controlling corticosteroid production. In adipose tissue, the activation of the MR by glucocorticoids (GC) and aldosterone affects important processes such as adipocyte differentiation, oxidative stress, autophagic flux, adipokine expression as well as local production of GC through upregulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28911177/deoxycorticosterone-salt-mediated-cardiac-inflammation-and-fibrosis-are-dependent-on-functional-clock-signaling-in-male-mice
#10
Elizabeth K Fletcher, James Morgan, David R Kennaway, Laura A Bienvenu, Amanda J Rickard, Lea M D Delbridge, Peter J Fuller, Colin D Clyne, Morag J Young
Activation of the mineralocorticoid receptor (MR) promotes inflammation, fibrosis, and hypertension. Clinical and experimental studies show that MR antagonists have significant therapeutic benefit for all-cause heart failure; however, blockade of renal MRs limits their widespread use. Identification of key downstream signaling mechanisms for the MR in the cardiovascular system may enable development of targeted MR antagonists with selectivity for pathological MR signaling and lower impact on physiological renal electrolyte handling...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28886589/role-of-fkbp51-in-the-modulation-of-the-expression-of-the-corticosteroid-receptors-in-bovine-thymus-following-glucocorticoid-administration
#11
L Starvaggi Cucuzza, B Biolatti, F E Scaglione, F T Cannizzo
The aim of this work was to study the transcriptional effects of glucocorticoids on corticosteroid hormone receptors, prereceptors (11β-hydroxysteroid dehydrogenase 1 and 2, 11β-HSD1 and 2), and chaperones molecules regulating intracellular trafficking of the receptors (FKBP51 and FKBP52) in thymus of veal calves. Moreover, the expression of FKBP51 and FKBP52 gene were investigated in beef cattle thymus. In the cervical thymus of veal calves, dexamethasone administration in combination with estradiol decreased FKBP51 expression (P < 0...
August 8, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28871373/-acute-and-chronic-heart-failure
#12
K-P Kresoja, G Schmidt, B Kherad, F Krackhardt, F Spillmann, C Tschöpe
The initial therapy of chronic heart failure is still based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and in specific cases mineralocorticoid receptor antagonists. The new European Society of Cardiology (ESC) guidelines published in 2016 introduced angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan (LCZ 696) as new therapeutic agents in patients with chronic and progressive heart failure. New subgroup analyses for LCZ 696 have been published showing a beneficial effect in the context of various comorbidities, such as renal insufficiency, diabetes and hypotension...
September 4, 2017: Herz
https://www.readbyqxmd.com/read/28866683/the-avian-hippocampal-formation-and-the-stress-response
#13
Tom V Smulders
Though widely studied for its function in memory and navigation, the hippocampal formation (HF) in mammals also plays an important role in regulating the stress response. If this is an ancestral feature of the hippocampus, then it is likely that the avian HF plays a similar role. Indeed, the avian HF strongly expresses both mineralocorticoid and glucocorticoid receptors, and has indirect projections to the paraventricular nucleus of the hypothalamus, which controls the hypothalamic-pituitary-adrenal (HPA) axis...
2017: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/28866130/differential-effects-of-imipramine-and-cort118335-glucocorticoid-receptor-modulator-mineralocorticoid-receptor-antagonist-on-brain-endocrine-stress-responses-and-depression-like-behavior-in-female-rats
#14
Elizabeth T Nguyen, Jody L Caldwell, Joshua Streicher, Valentina Ghisays, Nikolaus J Balmer, Christina M Estrada, Matia B Solomon
Depression is commonly associated with hypothalamic-pituitary adrenal (HPA) axis dysfunction that primarily manifests as aberrant glucocorticoid secretion. Glucocorticoids act on Type I mineralocorticoid (MR) and Type II glucocorticoid receptors (GR) to modulate mood and endocrine responses. Successful antidepressant treatment normalizes HPA axis function, in part due to modulatory effects on MR and GR in cortico-limbic structures. Although women are twice as likely to suffer from depression, little is known about how antidepressants modulate brain, endocrine, and behavioral stress responses in females...
September 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28865712/microrna-31-promotes-adverse-cardiac-remodeling-and-dysfunction-in-ischemic-heart-disease
#15
Eliana C Martinez, Shera Lilyanna, Peipei Wang, Leah A Vardy, Xiaofei Jiang, Arunmozhiarasi Armugam, Kandiah Jeyaseelan, Arthur Mark Richards
RATIONALE: Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets. OBJECTIVE: We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo. METHODS AND RESULTS: Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats...
September 1, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28862266/genomic-and-epigenomic-mechanisms-of-glucocorticoids-in-the-brain
#16
REVIEW
Jason D Gray, Joshua F Kogan, Jordan Marrocco, Bruce S McEwen
Following the discovery of glucocorticoid receptors in the hippocampus and other brain regions, research has focused on understanding the effects of glucocorticoids in the brain and their role in regulating emotion and cognition. Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Allostatic overload, which can occur during chronic stress, can reshape the hypothalamic-pituitary-adrenal axis through epigenetic modification of genes in the hippocampus, hypothalamus and other stress-responsive brain regions...
September 1, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28859848/chronic-in-vivo-nitric-oxide-deficiency-impairs-cardiac-functional-recovery-after-ischemia-in-female-but-not-male-mice
#17
Laura A Bienvenu, James Morgan, Melissa E Reichelt, Lea M D Delbridge, Morag J Young
Nitric oxide (NO) is an important regulator of cardiac function and plays a key role in ischemic cardioprotection. The role of chronic NO deficiency in coordinating ischemic vulnerability in female myocardium has not been established. The aim of this study was to determine the influence of chronic in vivo NO synthase inhibition in modulating ex vivo ischemia-reperfusion responses in female hearts (relative to males). Mice were subjected to l-NAME (l-N(G)-Nitroarginine-methyl-ester) treatment in vivo for 8weeks...
August 30, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28855452/galectin-3-and-the-mineralocorticoid-receptor-antagonist-canrenone-in-mild-heart-failure
#18
Francesco Clemenza, Serge Masson, Pier Giulio Conaldi, Daniele Di Carlo, Alessandro Boccanelli, Gian Francesco Mureddu, Lucio Gonzini, Donata Lucci, Aldo P Maggioni, Andrea Di Lenarda, Enrico B Nicolis, Massimo Vanasia, Roberto Latini
BACKGROUND: Galectin-3 (Gal-3) is involved in collagen deposition and inflammation and is a prognostic biomarker in heart failure (HF).Methods and Results:Gal-3 and other markers of fibrosis or cardiac stress were measured serially in 413 patients with mild HF randomized to the mineralocorticoid receptor antagonist canrenone or placebo to evaluate treatment effect and association with clinical outcome. Gal-3 increased slightly over 6 months in both arms of the study and was associated with clinical endpoints...
August 31, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28855315/eplerenone-prevented-obesity-induced-inflammasome-activation-and-glucose-intolerance
#19
Tsutomu Wada, Akari Ishikawa, Eri Watanabe, Yuto Nakamura, Yusuke Aruga, Hayate Hasegawa, Yasuhiro Onogi, Hiroe Honda, Yoshinori Nagai, Kiyoshi Takatsu, Yoko Ishii, Masakiyo Sasahara, Daisuke Koya, Hiroshi Tsuneki, Toshiyasu Sasaoka
Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance, and enhanced energy metabolism...
August 30, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28855243/update-on-angiotensin-ii-new-endocrine-connections-between-the-brain-adrenal-glands-and-the-cardiovascular-system
#20
Frans Leenen, Mordecai P Blaustein, John Hamlyn
In the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na+] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels, and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits, and maintains/further increases activity of angiotensinergic pathways...
August 30, 2017: Endocrine Connections
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