Structural determinants of ligand binding to the mineralocorticoid receptor

Huyet, J.; Pinon, Grégory; Fay, Michèle; Rafestin‐Oblin, Marie‐Edith; Fagart, Jérôme

doi:10.1016/j.mce.2011.07.035

Cited by 39 publications

(29 citation statements)

References 65 publications

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“…Further, since the interaction between the N-and C-terminal domains is ligand-specific, MR undergoes ligand-specific conformational changes. This conformational change might affect the interaction with co-regulator proteins which would induce the ligand-specificity (Pippal et al, 2011;Huyet et al, 2012;Fuller et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning and characterization of the corticoid receptors from the American alligator

Oka

Kohno

Urushitani

et al. 2013

Molecular and Cellular Endocrinology

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Although extensively studied in mammals and some non-mammalian species, the molecular mechanisms of corticosteroid hormone (glucocorticoids and mineralocorticoids) action are poorly understood in reptiles. Here, we have evaluated hormone receptor-ligand interactions in the American alligator (Alligator mississippiensis), following the isolation of cDNAs encoding a glucocorticoid receptor (GR) and a mineralocorticoid receptor (MR). The full-length alligator GR (aGR) and aMR cDNAs were obtained using 5' and 3' rapid amplification cDNA ends (RACE). The deduced amino acid sequences exhibited high identity to the chicken orthologs (aGR: 83%; aMR: 90%). Using transient transfection assays of mammalian cells, both aGR and aMR proteins displayed corticosteroid-dependent activation of transcription from keto-steroid hormone responsive, murine mammary tumor virus promoters. We further compared the ligand-specifity of human, chicken, Xenopus, and zebrafish GR and MR. We found that the alligator and chicken GR/MR have very similar amino acid sequences, and this translates to very similar ligand specificity. This is the first report of the full-coding regions of a reptilian GR and MR, and the examination of their transactivation by steroid hormones.3

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Section: Discussionmentioning

confidence: 99%

Molecular cloning and characterization of the corticoid receptors from the American alligator

Oka

Kohno

Urushitani

et al. 2013

Molecular and Cellular Endocrinology

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“…For this review we have selected eight genes that when mutated or deleted cause the most severe phenotypes in humans (FIGURE 6B), indicating that they are coding for proteins that are limiting factors in the aldosterone signaling pathway and critical in establishing vectorial reabsorption of sodium in ASDN. These genes code for 1) the MR (156,158,235); 2) 11␤-HSD2 (48,240), which protects the MR from illicit occupancy by glucocorticoids (cortisol or corticosterone); 3) ENaC ␣-, ␤-, or ␥-subunit (174,278); and 4) Na ϩ -K ϩ -ATPase ␣-, ␤-, and ␥-subunit (118,119). Mutations of the regulatory subunit (␥ or FXYD2) are compatible with survival (115) unlike lossof-function mutations on ␣␤, which have not been observed in humans because they are likely to be embryonic lethal according to gene inactivation in transgenic mouse models (20).…”

Section: Genetic Evidence For the Limiting Stepsmentioning

confidence: 99%

“…Research from several laboratories (32,33,36,121,158) provided insights into the structural basis for changes in the response of the MR and GR to corticosteroids. In particular, three sites in vertebrate CR, MR, and GR provide clues to the evolution of the MR and GR that led to their divergence in their specificity for corticosteroids.…”

Section: Structural and Sequence Analysis Of Three Key Sites That Infmentioning

confidence: 99%

Epithelial Sodium Transport and Its Control by Aldosterone: The Story of Our Internal Environment Revisited

Rossier

Baker

Studer

2015

Physiological Reviews

222

249

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Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

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“…An injectable preparation (potassium canrenoate) is more widely available. Of note, progesterone is a natural MRA (Huyet et al, 2012). Eplerenone (9-11a-epoxymexrenone), a second generation MRA, was developed by Ciba-Geigy (Basel, Switzerland) and launched by Pfizer (New York, NY) in 2002 for the treatment of hypertension and heart failure MR antagonism for:…”

Section: A Steroidal Compoundsmentioning

confidence: 99%

“…In the kidney, this should induce permanent maximal sodium retention, independent of plasma aldosterone levels. The main mechanism ensuring in vivo mineralocorticoid selectivity involves coexpression of MR and the enzyme 11b hydroxysteroid dehydrogenase type 2 (11HSD2), that metabolizes circulating glucocorticoid hormones (cortisol in humans, corticosterone in rodents) into inactive 11-dehydro-derivatives (cortisone, 11-dehydrocorticosterone) with very low affinity for the MR (Farman and Rafestin-Oblin, 2001;Huyet et al, 2012;Odermatt and Kratschmar, 2012). Other mechanisms are important for mineralocorticoid selectivity (i.e., the events that explain the higher efficacy of MR-aldosterone versus MR-glucocorticoid complexes) (Farman and Rafestin-Oblin, 2001;Viengchareun et al, 2007;Fuller et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

2015

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Structural determinants of ligand binding to the mineralocorticoid receptor

Cited by 39 publications

References 65 publications

Molecular cloning and characterization of the corticoid receptors from the American alligator

Molecular cloning and characterization of the corticoid receptors from the American alligator

Epithelial Sodium Transport and Its Control by Aldosterone: The Story of Our Internal Environment Revisited

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

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