Genomes and Genes
Summary: Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.
- Sainte Marie Y, Toulon A, Paus R, Maubec E, Cherfa A, Grossin M, et al. Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia. Am J Pathol. 2007;171:846-60 pubmed..This new mouse model reveals novel biological roles of MR signaling and offers an instructive tool for dissecting nonclassical functions of MR signaling in epidermal, hair follicle, and ocular physiology...
- Hodgson Z, Meddle S, Roberts M, Buchanan K, Evans M, Metzdorf R, et al. Spatial ability is impaired and hippocampal mineralocorticoid receptor mRNA expression reduced in zebra finches (Taeniopygia guttata) selected for acute high corticosterone response to stress. Proc Biol Sci. 2007;274:239-45 pubmed publisher..Together, these findings provide evidence to suggest that stress hormones have important regulatory roles in avian spatial cognition...
- Khaksari M, Rashidy Pour A, Vafaei A. Central mineralocorticoid receptors are indispensable for corticosterone-induced impairment of memory retrieval in rats. Neuroscience. 2007;149:729-38 pubmed..These findings provide evidence for the view that glucocorticoids impair memory retrieval through nongenomic mechanisms involving an interaction with central MRs. ..
- Guo C, Martinez Vasquez D, Mendez G, Toniolo M, Yao T, Oestreicher E, et al. Mineralocorticoid receptor antagonist reduces renal injury in rodent models of types 1 and 2 diabetes mellitus. Endocrinology. 2006;147:5363-73 pubmed..Thus, these data suggest that MR activation is a critical factor in the early pathogenesis of renal disease in both type 1 and type 2 diabetes mellitus. ..
- Ito K, Hirooka Y, Sunagawa K. Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload. J Hypertens. 2010;28:1449-58 pubmedIn a pressure overload model, sympathetic activity is augmented in response to salt intake. Mineralocorticoid receptors and epithelial Na channels (ENaCs) are thought to contribute to Na-processing, but the underlying mechanism is ..
- Nielsen F, Jensen B, Marcussen N, Skøtt O, Bie P. Inhibition of mineralocorticoid receptors with eplerenone alleviates short-term cyclosporin A nephrotoxicity in conscious rats. Nephrol Dial Transplant. 2008;23:2777-83 pubmed publisher..We conclude that the aldosterone-MR pathway contributes markedly to the renal toxicity induced by this calcineurin inhibitor. ..
- Balsamo A, Cicognani A, Gennari M, Sippell W, Menabò S, Baronio F, et al. Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1. Eur J Endocrinol. 2007;156:249-56 pubmed..The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease caused by mutations in the human mineralocorticoid receptor gene (NR3C2)...
- Grossmann C, Krug A, Freudinger R, Mildenberger S, Voelker K, Gekle M. Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter. Am J Physiol Endocrinol Metab. 2007;292:E1790-800 pubmed..Our results indicate that aldosterone leads to enhanced EGFR expression via an interaction with the EGFR promoter, which is MR specific and could contribute to the aldosterone-induced increase in fibronectin abundance. ..
- Talge N, Neal C, Glover V. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why?. J Child Psychol Psychiatry. 2007;48:245-61 pubmed
- Caprio M, Feve B, Claës A, Viengchareun S, Lombes M, Zennaro M. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J. 2007;21:2185-94 pubmed..to their role in controlling water and salt homeostasis, recent work suggests that aldosterone and mineralocorticoid receptors (MR) may be involved in adipocyte biology...
- Ising M, Depping A, Siebertz A, Lucae S, Unschuld P, Kloiber S, et al. Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci. 2008;28:389-98 pubmed publisher..This reaction pattern suggests that subjects carrying these variants are at risk of displaying chronically elevated cortisol levels after repeated stress constituting a risk factor for stress-related diseases. ..
- Funder J, Mihailidou A. Aldosterone and mineralocorticoid receptors: Clinical studies and basic biology. Mol Cell Endocrinol. 2009;301:2-6 pubmed publisher..and expansion) of our previous concepts of the basic (patho)physiology of aldosterone and mineralocorticoid receptors (MR)...
- Mihailidou A, Loan Le T, Mardini M, Funder J. Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. Hypertension. 2009;54:1306-12 pubmed publisher..The present study shows that cardiac damage is aggravated by activation of mineralocorticoid receptors by aldosterone or cortisol or of glucocorticoid receptors by dexamethasone...
- Nakamura Y, Suzuki S, Suzuki T, Ono K, Miura I, Satoh F, et al. MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling. Am J Pathol. 2006;169:362-71 pubmed
- Rickard A, Morgan J, Tesch G, Funder J, Fuller P, Young M. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension. 2009;54:537-43 pubmed publisher..b>Mineralocorticoid receptors are expressed in many cell types of the cardiovascular system, including monocytes/macrophages and ..
- Caprio M, Newfell B, la Sala A, Baur W, Fabbri A, Rosano G, et al. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res. 2008;102:1359-67 pubmed publisher..These studies describe a novel mechanism by which aldosterone may influence ischemic cardiovascular events and support a new explanation for the decrease in ischemic events in patients treated with aldosterone antagonists. ..
- Funder J. Aldosterone and mineralocorticoid receptors in the cardiovascular system. Prog Cardiovasc Dis. 2010;52:393-400 pubmed publisherAldosterone is currently thought to exert its physiologic effects by activating epithelial mineralocorticoid receptors, and its pathologic effects on the cardiovascular system via mineralocorticoid receptors in the heart and blood ..
- Gallo L, Ghini A, Piwien Pilipuk G, Galigniana M. Differential recruitment of tetratricorpeptide repeat domain immunophilins to the mineralocorticoid receptor influences both heat-shock protein 90-dependent retrotransport and hormone-dependent transcriptional activity. Biochemistry. 2007;46:14044-57 pubmed..Hsp90 complex to positively regulate the mineralocorticoid effect. ..
- Rozeboom A, Akil H, Seasholtz A. Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Proc Natl Acad Sci U S A. 2007;104:4688-93 pubmed..These findings point to the importance of the MR:GR ratio in the control of emotional reactivity. ..
- Tirard M, Almeida O, Hutzler P, Melchior F, Michaelidis T. Sumoylation and proteasomal activity determine the transactivation properties of the mineralocorticoid receptor. Mol Cell Endocrinol. 2007;268:20-9 pubmed..The data suggest that the overall transcriptional activity of MR can be modulated by its sumoylation potential as well as the sumoylation level of MR-interacting proteins, and requires the continuous function of the proteasome. ..
- Felder R. Mineralocorticoid receptors, inflammation and sympathetic drive in a rat model of systolic heart failure. Exp Physiol. 2010;95:19-25 pubmed publisherAppreciation for the role of aldosterone and mineralocorticoid receptors in cardiovascular disease is accelerating rapidly...
- Rogerson F, Yao Y, Elsass R, Dimopoulos N, Smith B, Fuller P. A critical region in the mineralocorticoid receptor for aldosterone binding and activation by cortisol: evidence for a common mechanism governing ligand binding specificity in steroid hormone receptors. Mol Endocrinol. 2007;21:817-28 pubmed
- Jaffe I, Tintut Y, Newfell B, Demer L, Mendelsohn M. Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler Thromb Vasc Biol. 2007;27:799-805 pubmed..These data provide a mechanistic link between hormone-mediated VSMC MR activation and vascular calcification, two processes associated with increased risk of cardiovascular ischemic events in humans. ..
- Ronzaud C, Loffing J, Bleich M, Gretz N, Grone H, Schutz G, et al. Impairment of sodium balance in mice deficient in renal principal cell mineralocorticoid receptor. J Am Soc Nephrol. 2007;18:1679-87 pubmed
- Baker M, Chandsawangbhuwana C, Ollikainen N. Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors. BMC Evol Biol. 2007;7:24 pubmed..A mutation corresponding to His-950 in human MR may have been important in physiological changes associated with emergence of Old World monkeys from prosimians. ..
- Gomez Sanchez E. Central mineralocorticoid receptors and cardiovascular disease. Neuroendocrinology. 2009;90:245-50 pubmed publisher..MR that pertain to the central modulation of cardiovascular function and health are addressed herein. ..
- Wong S, Brennan F, Young M, Fuller P, Cole T. A direct effect of aldosterone on endothelin-1 gene expression in vivo. Endocrinology. 2007;148:1511-7 pubmed..tissues such as the kidney and colon, via a pathway involving the activation of intracellular mineralocorticoid receptors (MR), induction of specific target genes, and a subsequent increase in sodium channel activity...
- Roubos E, Kuribara M, Kuipers Kwant F, Coenen T, Meijer K, Cruijsen P, et al. Dynamics of glucocorticoid and mineralocorticoid receptors in the Xenopus laevis pituitary pars intermedia. Ann N Y Acad Sci. 2009;1163:292-5 pubmed publisher..Corticosterone did not affect short-term intracellular calcium dynamics and alpha-melanophore-stimulating hormone secretion, suggesting a role for GR and MR in long-term processes in the melanotropes. ..
- Odermatt A, Atanasov A. Mineralocorticoid receptors: emerging complexity and functional diversity. Steroids. 2009;74:163-71 pubmed publisher..This review addresses the emerging new view of the complex mechanisms underlying MR specificity of action, with a diversity of physiological roles and functions in different mineralocorticoid-responsive tissues. ..
- Olijslagers J, de Kloet E, Elgersma Y, van Woerden G, Joels M, Karst H. Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors. Eur J Neurosci. 2008;27:2542-50 pubmed publisher..of miniature excitatory postsynaptic currents in mouse CA1 pyramidal neurons via membrane-located mineralocorticoid receptors (MRs)...
- Patel P, Katz M, Karssen A, Lyons D. Stress-induced changes in corticosteroid receptor expression in primate hippocampus and prefrontal cortex. Psychoneuroendocrinology. 2008;33:360-7 pubmed publisher..053). These results provide new information on regional differences and the long-term effects of stress on MR and GR distributions in corticolimbic regions that control cognitive and neuroendocrine functions. ..
- Funder J. Minireview: Aldosterone and mineralocorticoid receptors: past, present, and future. Endocrinology. 2010;151:5098-102 pubmed publisher..control of its secretion by ACTH, angiotensin II, and plasma [K(+)]; its action via intracellular mineralocorticoid receptors to promote DNA-directed; RNA-mediated synthesis of proteins responsible for its epithelial effects; and ..
- Yokota K, Shibata H, Kurihara I, Kobayashi S, Suda N, Murai Takeda A, et al. Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9. J Biol Chem. 2007;282:1998-2010 pubmed..These findings support a physiological role of Ubc9 as a transcriptional MR coactivator, beyond the known SUMO E2-conjugating enzyme. ..
- Riepe F, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, et al. Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006;91:4552-61 pubmed..Pseudohypoaldosteronism type 1 (PHA1) is a rare salt-wasting syndrome. Mutations in the NR3C2 gene coding for the mineralocorticoid receptor (MR) cause autosomal dominant PHA1...
- DeRijk R, Wüst S, Meijer O, Zennaro M, Federenko I, Hellhammer D, et al. A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. J Clin Endocrinol Metab. 2006;91:5083-9 pubmedb>Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes...
- Pujo L, Fagart J, Gary F, Papadimitriou D, Claës A, Jeunemaitre X, et al. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007;28:33-40 pubmed..The other patients without MR mutations might have different diseases resembling to PHA1 in the neonatal period, which could be identified by extensive clinical and functional exploration...
- Funder J. The role of aldosterone and mineralocorticoid receptors in cardiovascular disease. Am J Cardiovasc Drugs. 2007;7:151-7 pubmedThe roles of aldosterone and mineralocorticoid receptors in cardiovascular disease have been expanded, refined, and distinguished over the past decade...
- Proszkowiec Weglarz M, Porter T. Functional characterization of chicken glucocorticoid and mineralocorticoid receptors. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1257-68 pubmed publisher..Corticosteroids induced translocation of both receptors into the nucleus. The functional properties of cGR and cMR determined in this study will be helpful in defining the physiological roles of GR and MR in avian species. ..
- Brinks V, Berger S, Gass P, de Kloet E, Oitzl M. Mineralocorticoid receptors in control of emotional arousal and fear memory. Horm Behav. 2009;56:232-8 pubmed publisher..We propose that such a disbalance in MR:GR functions in MR(CaMKCre) mice provides the conditions for an animal model for anxiety-related disorders. ..
- Huang B, White R, Jeng A, Leenen F. Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol. 2009;296:R994-R1000 pubmed publisher..These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension. ..
- Takeda A, Pinon G, Bens M, Fagart J, Rafestin Oblin M, Vandewalle A. The synthetic androgen methyltrienolone (r1881) acts as a potent antagonist of the mineralocorticoid receptor. Mol Pharmacol. 2007;71:473-82 pubmed
- Milik E, Szczepanska Sadowska E, Maslinski W, Cudnoch Jedrzejewska A. Enhanced expression of mineralocorticoid receptors in the heart after the myocardial infarct in rats. J Physiol Pharmacol. 2007;58:745-55 pubmed..Because increased synthesis of mineralocorticoid receptors (MR) is one of the putative factors determining pathogenic effects of mineralocorticoids we decided to ..
- Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49:355-64 pubmed..Aldosterone can directly modulate podocyte function, possibly through the induction of oxidative stress and Sgk1. ..
- Huyet J, Pinon G, Fay M, Fagart J, Rafestin Oblin M. Structural basis of spirolactone recognition by the mineralocorticoid receptor. Mol Pharmacol. 2007;72:563-71 pubmed..Thus, the MR(S810L) structure may provide a powerful tool for designing new, more effective, MR antagonists. ..
- Ge R, Dong Q, Sottas C, Latif S, Morris D, Hardy M. Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005;243:35-42 pubmed..Glucocorticoids bind to both glucocorticoid receptors (GRs) and to mineralocorticoid receptors (MRs)...
- Crochemore C, Lu J, Wu Y, Liposits Z, Sousa N, Holsboer F, et al. Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation. Mol Psychiatry. 2005;10:790-8 pubmed..These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR. ..
- Jaffe I, Mendelsohn M. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res. 2005;96:643-50 pubmed
- Fagart J, Huyet J, Pinon G, Rochel M, Mayer C, Rafestin Oblin M. Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol. 2005;12:554-5 pubmed..These structures, the first for MR, identify the specific contacts created by Leu810 and clarify the mechanism of activation of MR S810L. ..
- Yoshida M, Ma J, Tomita T, Morikawa N, Tanaka N, Masamura K, et al. Mineralocorticoid receptor is overexpressed in cardiomyocytes of patients with congestive heart failure. Congest Heart Fail. 2005;11:12-6 pubmedb>Mineralocorticoid receptors (MRs) have been identified in the human cardiovascular tissues...
- Garcia A, Steiner B, Kronenberg G, Bick Sander A, Kempermann G. Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Aging Cell. 2004;3:363-71 pubmed..This course and variability of receptor expression in aging might help to explain differential vulnerability of adult neural precursor cells to corticoid-mediated influences. ..
- Bledsoe R, Madauss K, Holt J, Apolito C, Lambert M, Pearce K, et al. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005;280:31283-93 pubmed..Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone. ..
- Pascual Le Tallec L, Simone F, Viengchareun S, Meduri G, Thirman M, Lombes M. The elongation factor ELL (eleven-nineteen lysine-rich leukemia) is a selective coregulator for steroid receptor functions. Mol Endocrinol. 2005;19:1158-69 pubmed..These findings allow us to propose the concept of "transcriptional selector" for ELL on steroid receptor transcriptional functions. ..
- Marissal Arvy N, Lombes M, Petterson J, Moisan M, Mormede P. Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat. J Biol Chem. 2004;279:39232-9 pubmed..This work illustrates the interest of a pluristrategic approach to explore the mineralocorticoid receptor signaling pathway and its implication in the regulation of hydroelectrolytic homeostasis and blood pressure. ..
- Moldow R, Beck K, Weaver S, Servatius R. Blockage of glucocorticoid, but not mineralocorticoid receptors prevents the persistent increase in circulating basal corticosterone concentrations following stress in the rat. Neurosci Lett. 2005;374:25-8 pubmed..GR activation during stressor exposure appears to be necessary for the development of subsequent basal corticosterone elevations. ..
- Ouvrard Pascaud A, Sainte Marie Y, Benitah J, Perrier R, Soukaseum C, Nguyen Dinh Cat A, et al. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation. 2005;111:3025-33 pubmed..Our results indicate that cardiac MR triggers cardiac arrhythmias, suggesting novel opportunities for prevention of arrhythmia-related sudden death. ..
- Funder J. Mineralocorticoid receptors: distribution and activation. Heart Fail Rev. 2005;10:15-22 pubmedb>Mineralocorticoid receptors (MR) bind both mineralocorticoids and glucocorticoids with high affinity (deoxycorticosterone = corticosterone >/= aldosterone = cortisol), and are found in both Na(+) transporting epithelia (e.g...
- Nagai Y, Miyata K, Sun G, Rahman M, Kimura S, Miyatake A, et al. Aldosterone stimulates collagen gene expression and synthesis via activation of ERK1/2 in rat renal fibroblasts. Hypertension. 2005;46:1039-45 pubmed..These results suggest that aldosterone stimulates collagen gene expression and synthesis via MR-mediated ERK1/2 activation in renal fibroblasts, which may contribute to the progression of aldosterone-induced tubulointerstitial fibrosis. ..
- Hu X, Funder J. The evolution of mineralocorticoid receptors. Mol Endocrinol. 2006;20:1471-8 pubmed
- Wang X, Skelley L, Cade R, Sun Z. AAV delivery of mineralocorticoid receptor shRNA prevents progression of cold-induced hypertension and attenuates renal damage. Gene Ther. 2006;13:1097-103 pubmed..1) AAV delivery of MR-shRNA effectively silenced MR in vivo. (2) RNA interference inhibition of MR may open a new avenue for the long-term control of hypertension and renal damage. ..
- Bridgham J, Carroll S, Thornton J. Evolution of hormone-receptor complexity by molecular exploitation. Science. 2006;312:97-101 pubmed..Our results indicate that tight interactions can evolve by molecular exploitation-recruitment of an older molecule, previously constrained for a different role, into a new functional complex. ..
- Funder J. RALES, EPHESUS and redox. J Steroid Biochem Mol Biol. 2005;93:121-5 pubmed..Finally, the pathophysiologic roles of always-occupied MR in 'unprotected' tissues such as cardiomyocytes or neurons in response to altered intracellular redox status remain to be explored. ..