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Details for receptor: mineralcorticoid receptor

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EndoNet ID: ENR00662

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Synonyms

  • mineralcorticoid receptor
  • NR3C2
  • MR

General information

  • Ubiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes. [1]
  • Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. [1]
  • Type 1 MRs, which were first described in the renal cytosol are abundant in aldosterone target tissues including the kidney, colon and salivary glands. [2]
  • MRs in the CNS are concentrated predominantly in the hippocampus, the septum and the granular cells of the cerebellum.
  • The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. [1]
  • Cortisol and aldosterone have equal affinity for the MR. [3]

Links to other resources

UniProt P08235
Ensembl ENST00000358102

Binding hormones

  • corticosterone
  • cortisol
    • Given that aldosterone and cortisol have equivalent high affinity for the MR and that glucocorticoids circulate at much higher concentrations than aldosterone, under normal circumstances MR are largely occupied by cortisol. [4]
  • aldosterone
    (trough: blood
    )
    • Aldosterone specificity of MR in epithelial tissues and vascular smooth muscle cells is thus conferred by the enzyme 11β-hydroxysteroid dehydrogenase type 2. [5]

Anatomical structures with this receptor

  • kidney

    Induced phenotypes

    • Hypoaldosteronism
      • Hypoaldosteronism (mineralocorticoid defiency) may be due to inadequate stimulation of aldosterone secretion (hyporeninemic hypoaldosteronism), defects in adrenal synthesis of aldosterone, or resistance to the ion transport effects of aldosterone, such as are seen in pseudohypoaldosteronism type I. [6]
    • Primary Hyperaldosteronism
      • Primary aldosteronism, the most common form of endocrine hypertension is characterized by autonomous aldosterone production by the adrenal cortex (unilateral disease caused by aldosterone-producing adenoma and less frequently by unilateral adrenal hyperplasia; bilateral disease caused by idiopathic adrenal hyperplasia) resulting in hypertension with suppressed plasma renin, and, less frequently, in hypokalemia. [7]

  • cardiac_myocyte

  • epidermis

  • major_salivary_glands

  • hippocampus

  • cerebellum

  • macrophage

    Induced phenotypes

    • positive regulation of immune response
      • A recent study exploring the effect of corticosterone on isolated peritoneal macrophages has demonstrated that low corticosterone concentrations enhance macrophage immune functions. [8]
      • The effects of low corticosterone concentrations are mediated via MR. [8]
    • fibrosis
      • In renal disease models, reduced monocyte/macrophage infiltration is accompanied by a substantial reduction in fibrosis. MR signalling and macrophages appear to be important in inflammatory conditions in the kidney. [9]
      • Activation of an MR, in the context of inappropriate sodium status, has major cardiovascular pathophysiological consequences including cardiac fibrosis. [9]
      • In cardiac disease models, reduced monocyte/macrophage infiltration is accompanied by a substantial reduction in fibrosis. MR signalling and macrophages appear to be important in inflammatory conditions in the heart. [9]
      • Selective deletion of MR from macrophages protected against mineralocorticoid-mediated cardiac fibrosis, despite normal macrophage recruitment. [9]
    • production of molecular mediator involved in inflammatory
      • Inflammation may be a key mechanism translating MR signalling into cardiac and vascular remodelling. [9]
      • Mineralocorticoid/salt-induced pathology is characterised by an early vascular inflammatory response with elevated cardiac expression of inflammatory mediators such as monocytes/macrophages, MCP-1 and adhesion molecules (ICAM-1 and VCAM-1), prior to the onset of collagen deposition. [10]
      • mineralocorticoid/salt treatment is also associated with increased monocyte/macrophage infiltration and expression of inflammatory markers such as osteopontin, MCP-1, IL-6 and IL-1β in the kidney. [11]
      • MR antagonism prevents inflammation-induced peritoneal fibrosis and reduces macrophage infiltration and expression of MCP-1, TGF-β, PAI-1 and Sgk-1. [12]
    • atherosclerosis
      • Aldosterone treatment increases oxidative stress in macrophages derived from ApoE-deficient mice. [13]
      • Aldosterone activation of MR in endothelial cells specifically modulates ICAM-1 expression and promotes leukocyte adhesion, supporting a role for MR signalling in endothelial cells in the initial stages of atherosclerosis. These findings highlight a key role for both macrophage and endothelial MR signalling in atherosclerosis. [14]
    • hypertension
      • Activation of an MR, in the context of inappropriate sodium status, has major cardiovascular pathophysiological consequences including hypertension. [9]
      • Chronic inappropriate activation of an MR is well recognised to promote hypertension. Excess plasma mineralocorticoids promote sodium and water retention and potassium secretion leading to the maintenance of blood pressure at a higher set point. [15]
      • MR antagonists have been shown to be effective anti-hypertensive agents in essential hypertension, suggesting a role for MR signalling in hypertension. [16]

  • spleen

  • microglial_cell_in_central_nervous_system

    Induced phenotypes

    • positive regulation of immune response
      • Corticosterone exerts its immunostimulatory effects via both corticosteroid receptors in a concentration dependent manner in microglial cells. [17]

  • epithelial_cell

    Induced phenotypes

    • multicellular organismal water homeostasis
      • The classical effects of MR signalling are in epithelial tissues where activation promotes sodium reabsorption and potassium secretion, and is therefore crucial for salt and water retention. [18]
Reference