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

• These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels [11].
• ANP and cGMP rapidly (< 15 min) inhibited surface cell ALDO-induced MR nuclear translocation but did not affect crypt MR nuclear translocation [12].
• Atrial natriuretic peptide inhibits mineralocorticoid receptor function in rat colonic surface cells [12].
• Therefore, the effects of ANP and its second messenger cGMP on mineralocorticoid receptor (MR) function in rat colon surface and crypt cells were examined [12].
• Inhibition of cGMP-dependent protein kinase with KT5823 blocked the inhibitory effects of ANP and 8-Br-cGMP on surface cell ALDO binding and MR nuclear translocation [12].

Chemical compound and disease context of Nr3c2

• The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat [2].
• Furthermore, the hypertension produced by the oral administration of carbenoxolone or glycyrrhizic acid is blocked by the icv administration of RU 28318, an MR antagonist, at a dose below that which has an effect on blood pressure when infused subcutaneously [13].
• These studies suggest that altered MR- and GR-mediated mechanisms may contribute to the resistance of the W/Fu rat strain to steroid-induced hypertension [14].
• Our findings suggest that, in the amygdala, MR receptor-mediated mechanisms are likely involved in descending pathways onto lumbosacral spinal neurons that induce colorectal hypersensitivity to luminal distension [15].
• Animals bearing indwelling intracardiac venous catheters received a subcutaneous (s.c.) injection of either vehicle, the MR antagonist, RU 752 (0.5 or 5.0 mg/kg body weight), or the GR antagonist, RU 486 (0.5 or 5.0 mg/kg body weight) [16].

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

• Drospirenone displayed high affinity to PR and MR and low binding to AR, similar to progesterone [27].
• Aldosterone modulates glucocorticoid receptor binding in hippocampal cell cultures via the mineralocorticoid receptor [28].
• 5. In the cerebral cortex the chronical GH injection induced an increase in the number of antagonist binding sites and a decrease of their affinity, while the similar SRIF treatment led to an increase of the binding affinity without any change of M-receptor capacity [29].
• ZMS did not inhibit acetylcholinesterase nor did it occupy the binding sites of muscarinic acetylcholine receptor (M receptor), hence it is neither an cholinesterase inhibitor nor an agonist or antagonist of M receptors [30].

Co-localisations of Nr3c2

• We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron [31].
• In this respect 11 beta HSD2 colocalizes with the mineralocorticoid receptor [32].

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

• In contrast, early postnatal 11 beta-HSD-2 coincides with glucocorticoid receptor rather than mineralocorticoid receptor expression, and areas of expression are among the regions where glucocorticoids have been demonstrated to have profound effects upon neuronal division, growth and maturation [38].
• The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury [39].
• In mammals, 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity allows aldosterone occupancy of mineralocorticoid receptors (MR) by inactivating endogenous glucocorticoids [40].
• Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications [41].
• In addition to receptor binding studies, transactivation assays were carried out to investigate the effects of drospirenone and progesterone on AR-, GR-, and MR-mediated induction of transcription [27].

Analytical, diagnostic and therapeutic context of Nr3c2

• MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods [39].
• We showed a strong genetic linkage between the mineralocorticoid receptor genotype and sensitivity to adrenalectomy [21].
• Cell counts quantifying KA damage indicated increased CA3 vulnerability to KA insult after treatment with MR antagonist spironolactone but demonstrated no significant cell loss in any other group or region [42].
• Total RNA was extracted from the left ventricle of these rats, and examined for the expression levels of MR, 11beta-HSD2 and Collagen types 1 and 3 using reverse transcription real-time quantitative polymerase chain reaction employing the Light Cycler Instrument [2].
• The time-dependent action of corticosterone (10 mg/kg, s.c.) was analyzed in the same animal model revealing no changes in MR mRNA levels in the medial and lateral septal nuclei [43].

References