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Gene Review

Nr3c2  -  nuclear receptor subfamily 3, group C,...

Rattus norvegicus

Synonyms: MCR, MR, Mineralocorticoid receptor, Mlr, Nuclear receptor subfamily 3 group C member 2
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Disease relevance of Nr3c2

  • These data indicate that in Wistar rats, a chronic increase in CSF [Na+] may increase hypothalamic aldosterone and activate CNS pathways involving MR, and OLC, leading to increases in AT1-receptor and ACE densities in brain areas involved in cardiovascular regulation and hypertension [1].
  • Findings from the present study appear to demonstrate that MR and 11beta-HSD2 mRNA significantly rise in the left ventricle of M-SHRSP and increase of these mRNA is one of the cause of cardiac fibrosis [2].
  • In BN rats, body weight gain and fluid intake were insensitive to corticosterone deprivation, suggesting that MR-related mechanisms are constitutively active in this strain [3].
  • To examine the potential impact of ACR activation following traumatic brain injury (TBI), the current study assesses regulation of MR and GR expression and glucocorticoid levels following controlled cortical impact (CCI) [4].
  • We sought to establish the sequence of ionic events that link the initiating insult and MR to hypertrophy development [5].

Psychiatry related information on Nr3c2

  • We conclude that maternal food restriction during the perinatal period affects (1) the adult basal activity of the HPA axis with mainly opposite effects on hippocampal MR and GR gene expression and an increase in adenopituitary POMC gene expression, and (2) the responsiveness to water deprivation in adults [6].
  • However, the administration of aldosterone (ALDO), a selective MR agonist, was not sufficient to restore normal coping behavior [7].
  • The effect of nifedipine, a calcium channel antagonist, on changes in the density of glucocorticoid (GR) and/or mineralocorticoid receptors (MR), induced by long-term treatment with antidepressant drugs (imipramine and amitriptyline) or electroconvulsive shock (ECS) was investigated in the rat hippocampus [8].
  • After maternal deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise [9].
  • The effects of opiate dependence and antagonist-precipitated withdrawal on glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA levels in the rat brain were studied [10].

High impact information on Nr3c2


Chemical compound and disease context of Nr3c2


Biological context of Nr3c2

  • Here we demonstrate that EE induces GR, but not mineralocorticoid receptor (MR) gene expression in specific hippocampal subfields (CA1 and CA2) [17].
  • Structural evidence is presented for the identity of the type I corticosteroid binding site as the MR expressed in the brain [18].
  • The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are members of the intracellular receptor superfamily that bind as homodimers to the same hormone response elements (HREs) [19].
  • Finally, principal components analysis (PCA) suggests that neuronal AMPA and NMDA receptor composition may be regulated by MR and GR activation in a complex manner [20].
  • 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 [21].

Anatomical context of Nr3c2

  • Given the differential action of MR and GR in the central nervous system, it is important to elucidate how the trafficking of these receptors between cytoplasm and nucleus is regulated by ligand [22].
  • In COS-1 cells, expressing no endogenous corticosteroid receptors, the YFP-MR chimera was accumulated in the nucleus faster than the CFP-GR chimera in the presence of 10(-9) M CORT, while there was no significant difference in the nuclear accumulation rates in the presence of 10(-6) M CORT [22].
  • Previous studies indicate that the MR in the distal colon is localized to ion-transporting surface epithelial cells and non-epithelial neuroendocrine cells within the lamina propria [23].
  • In vitro, however, although NRK 52-E cells expressed the glucocorticoid receptor, corticosteroid regulation of Na,K-ATPase, even by dexamethasone, occurred exclusively via the MR, suggesting that accessory transcription factors required for glucocorticoid hormone action are absent in this cell line [24].
  • Furthermore, the spatially distinct patterns of expression of these isoforms suggest that in vivo there are two physiologically distinct populations of MR in the colon: the aldosterone selective MR in the epithelium and the nonselective MR in the nonepithelial cells within the lamina propria [23].

Associations of Nr3c2 with chemical compounds

  • On the other hand, in primary cultured hippocampal neurons expressing endogenous receptors, the nuclear accumulation rates of the YFP-MR chimera and CFP-GR chimera were nearly the same in the presence of both concentrations of CORT [22].
  • Dexamethasone, aldosterone, and high concentrations of B (1-10 microM) increased Na,K-ATPase alpha 1 and beta 1 messenger RNA (mRNA) levels, an effect that was inhibited by coincubation with the MR antagonist RU 26752, but not by the glucocorticoid receptor antagonist RU 38486 [24].
  • These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo [25].
  • This identification is supported by the anatomical distribution of MR mRNA, determined by in situ hybridization histochemistry, which parallels the steroid autoradiographic localization of the type I sites [18].
  • Therefore, we attempted to identify such coactivator complexes from HeLa nuclear extracts by biochemical purification using a glutathione S-transferase-MR AF-1a fusion protein [26].

Physical interactions of Nr3c2


Co-localisations of Nr3c2


Regulatory relationships of Nr3c2

  • We observed that the GR agonist RU 28362 blocks the attenuating action of the MR agonist aldosterone on responses to 3, 10 and 30 microM 5HT; RU 28362 by itself did not affect 5HT responses [33].
  • These findings suggest that activation of MR in the central nervous system plays a critical role in regulating TNF-alpha release in heart failure rats [34].
  • Our results show that CRH and AVP regulate MR and GR in hippocampus and anterior pituitary [35].
  • Thus, the present findings suggest that the adrenal cortical system through GR and MR participate in the control of neurotrophic factor signalling in a highly subregion- and cellular-dependent manner [36].
  • Corticosterone influences 5-HT1A receptor-mediated responses in the rat hippocampus in vitro: activation of the high affinity mineralocorticoid receptor suppresses 5-HT1A receptor-mediated hyperpolarization, while subsequent activation of lower affinity glucocorticoid receptors enhances the effect of 5-HT [37].

Other interactions of Nr3c2


Analytical, diagnostic and therapeutic context of Nr3c2


  1. Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats. Huang, B.S., Cheung, W.J., Wang, H., Tan, J., White, R.A., Leenen, F.H. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  2. The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat. Konishi, A., Tazawa, C., Miki, Y., Darnel, A.D., Suzuki, T., Ohta, Y., Suzuki, T., Tabayashi, K., Sasano, H. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  3. Strain differences in corticosteroid receptor efficiencies and regulation in Brown Norway and Fischer 344 rats. Marissal-Arvy, N., Mormède, P., Sarrieau, A. J. Neuroendocrinol. (1999) [Pubmed]
  4. Traumatic brain injury regulates adrenocorticosteroid receptor mRNA levels in rat hippocampus. McCullers, D.L., Sullivan, P.G., Scheff, S.W., Herman, J.P. Brain Res. (2002) [Pubmed]
  5. Mineralocorticoid receptor antagonism prevents the electrical remodeling that precedes cellular hypertrophy after myocardial infarction. Perrier, E., Kerfant, B.G., Lalevee, N., Bideaux, P., Rossier, M.F., Richard, S., Gómez, A.M., Benitah, J.P. Circulation (2004) [Pubmed]
  6. Altered control of the hypothalamo-pituitary-adrenal axis in adult male rats exposed perinatally to food deprivation and/or dehydration. Sebaai, N., Lesage, J., Vieau, D., Alaoui, A., Dupouy, J.P., Deloof, S. Neuroendocrinology (2002) [Pubmed]
  7. Biphasic effects of adrenal steroids on learned helplessness behavior induced by inescapable shock. Kademian, S.M., Bignante, A.E., Lardone, P., McEwen, B.S., Volosin, M. Neuropsychopharmacology (2005) [Pubmed]
  8. The effect of repeated combined treatment with nifedipine and antidepressant drugs or electroconvulsive shock on the hippocampal corticosteroid receptors in rats. Przegaliński, E., Budziszewska, B., Siwanowicz, J., Jaworska, L. Neuropharmacology (1993) [Pubmed]
  9. Differential and age-dependent effects of maternal deprivation on the hypothalamic-pituitary-adrenal axis of brown norway rats from youth to senescence. Workel, J.O., Oitzl, M.S., Fluttert, M., Lesscher, H., Karssen, A., de Kloet, E.R. J. Neuroendocrinol. (2001) [Pubmed]
  10. Selective down-regulation of hippocampal glucocorticoid receptors during opiate withdrawal. McNally, G.P., Akil, H. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  11. Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart. Hare, J.M., Kim, B., Flavahan, N.A., Ricker, K.M., Peng, X., Colman, L., Weiss, R.G., Kass, D.A. J. Clin. Invest. (1998) [Pubmed]
  12. Atrial natriuretic peptide inhibits mineralocorticoid receptor function in rat colonic surface cells. Schulman, G., Lindemeyer, R., Barman, A., Karnik, S., Bastl, C.P. J. Clin. Invest. (1996) [Pubmed]
  13. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Gomez-Sanchez, E.P., Gomez-Sanchez, C.E. Am. J. Physiol. (1992) [Pubmed]
  14. The resistance of the Wistar/Furth rat strain to steroid hypertension. Kayes, K., Ziegler, L., Yu, C.P., Brownie, A.C., Gallant, S. Endocr. Res. (1996) [Pubmed]
  15. Visceromotor and spinal neuronal responses to colorectal distension in rats with aldosterone onto the amygdala. Qin, C., Greenwood-Van Meerveld, B., Foreman, R.D. J. Neurophysiol. (2003) [Pubmed]
  16. Antagonism of type II, but not type I glucocorticoid receptors results in elevated basal luteinizing hormone release in male rats. Briski, K.P., Sylvester, P.W. Neuroendocrinology (1994) [Pubmed]
  17. Glucocorticoid receptor and NGFI-A gene expression are induced in the hippocampus after environmental enrichment in adult rats. Olsson, T., Mohammed, A.H., Donaldson, L.F., Henriksson, B.G., Seckl, J.R. Brain Res. Mol. Brain Res. (1994) [Pubmed]
  18. The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response. Arriza, J.L., Simerly, R.B., Swanson, L.W., Evans, R.M. Neuron (1988) [Pubmed]
  19. Steroid receptor heterodimerization demonstrated in vitro and in vivo. Liu, W., Wang, J., Sauter, N.K., Pearce, D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  20. Corticosteroid regulation of ion channel conductances and mRNA levels in individual hippocampal CA1 neurons. Nair, S.M., Werkman, T.R., Craig, J., Finnell, R., Joëls, M., Eberwine, J.H. J. Neurosci. (1998) [Pubmed]
  21. Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat. Marissal-Arvy, N., Lombès, M., Petterson, J., Moisan, M.P., Mormède, P. J. Biol. Chem. (2004) [Pubmed]
  22. Dynamic changes in subcellular localization of mineralocorticoid receptor in living cells: in comparison with glucocorticoid receptor using dual-color labeling with green fluorescent protein spectral variants. Nishi, M., Ogawa, H., Ito, T., Matsuda, K.I., Kawata, M. Mol. Endocrinol. (2001) [Pubmed]
  23. Epithelial cell localization of type 2 11 beta-hydroxysteroid dehydrogenase in rat and human colon. Whorwood, C.B., Ricketts, M.L., Stewart, P.M. Endocrinology (1994) [Pubmed]
  24. Regulation of sodium-potassium adenosine triphosphate subunit gene expression by corticosteroids and 11 beta-hydroxysteroid dehydrogenase activity. Whorwood, C.B., Ricketts, M.L., Stewart, P.M. Endocrinology (1994) [Pubmed]
  25. Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells. Mazak, I., Fiebeler, A., Muller, D.N., Park, J.K., Shagdarsuren, E., Lindschau, C., Dechend, R., Viedt, C., Pilz, B., Haller, H., Luft, F.C. Circulation (2004) [Pubmed]
  26. Ligand-selective potentiation of rat mineralocorticoid receptor activation function 1 by a CBP-containing histone acetyltransferase complex. Kitagawa, H., Yanagisawa, J., Fuse, H., Ogawa, S., Yogiashi, Y., Okuno, A., Nagasawa, H., Nakajima, T., Matsumoto, T., Kato, S. Mol. Cell. Biol. (2002) [Pubmed]
  27. The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Fuhrmann, U., Krattenmacher, R., Slater, E.P., Fritzemeier, K.H. Contraception. (1996) [Pubmed]
  28. Aldosterone modulates glucocorticoid receptor binding in hippocampal cell cultures via the mineralocorticoid receptor. O'Donnell, D., Meaney, M.J. Brain Res. (1994) [Pubmed]
  29. Muscarinic receptor activity change after prolonged treatment with growth hormone and somatostatin. Popova, J., Robeva, A., Zaharieva, S. Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (1990) [Pubmed]
  30. A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models. Hu, Y., Xia, Z., Sun, Q., Orsi, A., Rees, D. Brain Res. (2005) [Pubmed]
  31. Multiple patterns of 11 beta-hydroxysteroid dehydrogenase catalytic activity along the mammalian nephron. Kenouch, S., Coutry, N., Farman, N., Bonvalet, J.P. Kidney Int. (1992) [Pubmed]
  32. Localization of an 11 beta hydroxysteroid dehydrogenase activity to the distal nephron. Evidence for the existence of two species of dehydrogenase in the rat kidney. Mercer, W.R., Krozowski, Z.S. Endocrinology (1992) [Pubmed]
  33. Coordinative mineralocorticoid and glucocorticoid receptor-mediated control of responses to serotonin in rat hippocampus. Joëls, M., De Kloet, E.R. Neuroendocrinology (1992) [Pubmed]
  34. Central mineralocorticoid receptor blockade decreases plasma TNF-alpha after coronary artery ligation in rats. Francis, J., Weiss, R.M., Johnson, A.K., Felder, R.B. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  35. Chronic corticotropin-releasing hormone and vasopressin regulate corticosteroid receptors in rat hippocampus and anterior pituitary. Hügin-Flores, M.E., Steimer, T., Schulz, P., Vallotton, M.B., Aubert, M.L. Brain Res. (2003) [Pubmed]
  36. Gluco- and mineralocorticoid receptor-mediated regulation of neurotrophic factor gene expression in the dorsal hippocampus and the neocortex of the rat. Hansson, A.C., Cintra, A., Belluardo, N., Sommer, W., Bhatnagar, M., Bader, M., Ganten, D., Fuxe, K. Eur. J. Neurosci. (2000) [Pubmed]
  37. Acute rise in corticosterone facilitates 5-HT(1A) receptor-mediated behavioural responses. Meijer, O.C., Kortekaas, R., Oitzl, M.S., de Kloet, E.R. Eur. J. Pharmacol. (1998) [Pubmed]
  38. 11 Beta-hydroxysteroid dehydrogenase type 2 in the postnatal and adult rat brain. Robson, A.C., Leckie, C.M., Seckl, J.R., Holmes, M.C. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  39. Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability. Nishiyama, A., Yao, L., Fan, Y., Kyaw, M., Kataoka, N., Hashimoto, K., Nagai, Y., Nakamura, E., Yoshizumi, M., Shokoji, T., Kimura, S., Kiyomoto, H., Tsujioka, K., Kohno, M., Tamaki, T., Kajiya, F., Abe, Y. Hypertension (2005) [Pubmed]
  40. Glucocorticoid receptor, mineralocorticoid receptors, 11 beta-hydroxysteroid dehydrogenase-1 and -2 expression in rat brain and kidney: in situ studies. Roland, B.L., Krozowski, Z.S., Funder, J.W. Mol. Cell. Endocrinol. (1995) [Pubmed]
  41. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. Brady, L.S., Whitfield, H.J., Fox, R.J., Gold, P.W., Herkenham, M. J. Clin. Invest. (1991) [Pubmed]
  42. Adrenocorticosteroid receptor blockade and excitotoxic challenge regulate adrenocorticosteroid receptor mRNA levels in hippocampus. McCullers, D.L., Herman, J.P. J. Neurosci. Res. (2001) [Pubmed]
  43. Biphasic autoregulation of mineralocorticoid receptor mRNA in the medial septal nucleus by aldosterone. Hansson, A.C., Fuxe, K. Neuroendocrinology (2002) [Pubmed]
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