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Details on Person Mineralocorticoid receptor (MR or NR3C2) is a member of the ...
| Class:Id | Summation:9028597 |
|---|---|
| _displayName | Mineralocorticoid receptor (MR or NR3C2) is a member of the ... |
| _timestamp | 2020-03-02 22:16:22 |
| created | [InstanceEdit:9028579] Shamovsky, Veronica, 2017-11-09 |
| literatureReference | [LiteratureReference:9028631] Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands [LiteratureReference:9028614] Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor [LiteratureReference:9676796] Molecular evolution of the switch for progesterone and spironolactone from mineralocorticoid receptor agonist to antagonist [LiteratureReference:9676804] Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar [LiteratureReference:9676799] 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function [LiteratureReference:9676851] Aldosterone: its receptor, target genes, and actions [LiteratureReference:9036367] The multifaceted mineralocorticoid receptor [LiteratureReference:9676866] Aldosterone: intracellular receptors in human heart [LiteratureReference:9676885] Various actions of aldosterone: the kidney and beyond.. [LiteratureReference:9036349] Mineralocorticoid receptors: distribution and activation [LiteratureReference:9635725] Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion [LiteratureReference:9036390] Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor [LiteratureReference:9676883] The role of 11β-hydroxysteroid dehydrogenase type 2 in human hypertension [LiteratureReference:9036355] A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor [LiteratureReference:9676882] Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy [LiteratureReference:9676864] The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related [LiteratureReference:9677265] Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney [LiteratureReference:9677263] Effect of administered mineralocorticoids or ACTH in pregnant women. Attenuation of kaliuretic influence of mineralocorticoids during pregnancy [LiteratureReference:9677259] Normotensive blood pressure in pregnancy: the role of salt and aldosterone |
| modified | [InstanceEdit:9676801] Shamovsky, Veronica, 2020-02-20 [InstanceEdit:9676872] Shamovsky, Veronica, 2020-02-22 [InstanceEdit:9676980] Shamovsky, Veronica, 2020-02-24 [InstanceEdit:9677257] Shamovsky, Veronica, 2020-03-02 |
| text | Mineralocorticoid receptor (MR or NR3C2) is a member of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors (Gomez-Sanchez E et al. 2014). The major physiological function of NR3C2 is to regulate sodium reabsorption and potassium secretion in the epithelial cells, most notably in the kidney and colon and thus maintaining blood pressure as well as water and electrolyte homeostasis (Pearce D et al. 2003; Gomez-Sanchez E et al. 2014). It also plays important roles in non-epithelial tissues, such as cardiac myocytes, blood vessels, the hippocampus and adipose tissue (Bonvalet JP et al. 2005; Funder JW 2005; Caprio M et al. 2008; Lombès M 2009). While aldosterone is considered the primary physiological NR3C2 (MR) ligand in humans, other steroid hormones, including cortisol and progesterone, may function as tissue-specific endogenous agonists or antagonists of NR3C2 (Arriza JL et al. 1987; Quinkler M et al. 2002; Bledsoe RK et al. 2005; Ferrari P 2010). Progesterone binds NR3C2 with nearly the same affinity as do aldosterone and cortisol, but progesterone prevents NR3C2 activation and may act as a potential antagonist (Rupprecht, R et al. 1993; Quinkler M et al. 2002; Bledsoe RK et al. 2005). Progesterone circulates in low concentrations in comparison to aldosterone and cortisol in males and nonpregnant females and is inactivated by enzymes in aldosterone target epithelia of the kidney (Quinkler M et al. 2001). Although progesterone levels reach significant levels in pregnancy and the luteal phase of the estrus cycle, in healthy woman elevated levels of aldosterone and progesterone are thought to be tightly controlled to maintain fluid and electrolyte homeostasis (Ehrlich EN & Lindheimer MD 1972; Gennari-Moser C et al. 2014). The naturally occurring substitution of leucine for serine at codon 810 (S810L) of NR3C2 was found to alter receptor specificity with progesterone and other steroids lacking 21-hydroxyl groups, converting antagonists to agonists (Geller DS et al. 2000; Rafestin-Oblin ME et al. 2003). Structural and biochemical studies indicate that the mutation S810L results in the gain of a van der Waals interaction between helix 5 and helix 3 of NR3C2 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor (Geller DS et al. 2000; Bledsoe RK et al. 2005). Progesterone and aldosterone were equally effective in activating NR3C2 S810L variant causing pregnancy-related hypertension in patients (Geller DS et al. 2000). Although NR3C2 is highly conserved across vertebrate evolution, it binds progesterone as antagonists in human, but as agonists in zebrafish (Sugimoto A et al. 2016; Baker ME & Katsu Y 2017: Fuller PJ et al. 2019). Biochemical studies using chimeras between the zebrafish and human NR3C2 (MR) coupled with reciprocal site-directed mutagenesis and molecular dynamic (MD) simulation based on the crystal structures of the NR3C2 ligand-binding domain (LBD) identified a single amino acid difference in helix 8 of the LBD between the fish NR3C2 (Leu856) and human NR3C2 (Thr870) that mediates the switch, agonist to antagonist, in the response to progesterone and its derivative spironolactone (Fuller PJ et al. 2019). The Reactome event shows the interaction between mineralocorticoid receptor NR3C2 and its endogenous antagonist progesterone. |
| (summation) | [Reaction:9028656] Progesterone binds NR3C2 within the HSP90 chaperone complex [Homo sapiens] |
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No pathways have been reviewed or authored by Mineralocorticoid receptor (MR or NR3C2) is a member of the ... (9028597)
