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14 results on '"MESH: Hyperaldosteronism"'

1. Dysregulation of Aldosterone Secretion in Mast Cell–Deficient Mice

Author

Estelle Louiset, Hervé Lefebvre, Arnaud Arabo, Céline Duparc, Isabelle Boutelet, Hadrien-Gaël Boyer, Julien Wils, Sylvie Renouf, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), and Neuroendocrinologie cellulaire et moléculaire

Subjects
Male, 0301 basic medicine, MESH: Renin, mast cells, MESH: Adrenal Cortex Neoplasms, Adrenocortical adenoma, chemistry.chemical_compound, Primary aldosteronism, Renin, MESH: Animals, Aldosterone, renin–angiotensin system, Mice, Inbred BALB C, MESH: Mast Cells, Diet, Sodium-Restricted, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mast cell, Hyperaldosteronism, MESH: Hyperaldosteronism, MESH: Neoplasms, Experimental, medicine.anatomical_structure, Adrenocortical Adenoma, Female, MESH: Adrenocortical Adenoma, medicine.medical_specialty, hypertension, mice, food.diet, MESH: Mice, Inbred BALB C, Biology, Low sodium diet, Mast cell proliferation, 03 medical and health sciences, food, MESH: Mice, Inbred C57BL, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Renin–angiotensin system, Internal Medicine, medicine, Animals, MESH: Mice, MESH: Aldosterone, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Neoplasms, Experimental, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, adrenal, chemistry, MESH: Diet, Sodium-Restricted, hyperaldosteronism, low-sodium diet, MESH: Female
Abstract

Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell–deficient C57BL/6 Kit W-sh/W-sh mice in comparison with wild-type C57BL/6 mice. Kit W-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 Kit W-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction.

Published
2017
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2. Laparoscopic right partial adrenalectomy (with video)

Author

F. Guillon, J.M. Fabre, A. Cubisino, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Trieste, and Université de Montpellier (UM)

Subjects
medicine.medical_specialty, MESH: Humans, MESH: Middle Aged, business.industry, Partial adrenalectomy, MESH: Laparoscopy, Adrenalectomy, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, General Medicine, Middle Aged, Surgery, 03 medical and health sciences, MESH: Hyperaldosteronism, 0302 clinical medicine, 030220 oncology & carcinogenesis, Hyperaldosteronism, medicine, Humans, Laparoscopy, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS, MESH: Adrenalectomy
Abstract

International audience

Published
2020
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3. Adrenal Cortex Remodeling and Functional Zona Glomerulosa Hyperplasia in Primary Aldosteronism

Author

Arndt Benecke, Xavier Jeunemaitre, Estelle Louiset, José-Felipe Golib Dzib, Pierre-François Plouin, Sheerazed Boulkroun, Tchao Meatchi, Enzo Lalli, Laurence Amar, Benoit Samson-Couterie, Hervé Lefebvre, Maria-Christina Zennaro, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut des Hautes Etudes Scientifiques (IHES), IHES, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Hautes Etudes Scientifiques ( IHES ), Différenciation et communication neuronale et neuroendocrine ( DC2N ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), UNIROUEN - UFR Santé, Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université Côte d'Azur ( UCA ), Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] ( IRI ), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, MESH : Steroid 11-beta-Hydroxylase, MESH : Immunohistochemistry, MESH : Adrenal Cortex Neoplasms, MESH: Adrenal Cortex Neoplasms, MESH : Adrenal Cortex, chemistry.chemical_compound, 0302 clinical medicine, Primary aldosteronism, MESH : Female, Aldosterone, In Situ Hybridization, 0303 health sciences, MESH: Middle Aged, Adrenal cortex, MESH : In Situ Hybridization, Middle Aged, MESH : Adult, Hyperplasia, Immunohistochemistry, MESH : Hyperaldosteronism, MESH: Hyperaldosteronism, medicine.anatomical_structure, Female, Zona Glomerulosa, Adenoma, Adult, medicine.medical_specialty, MESH: Zona Glomerulosa, medicine.drug_class, MESH : Male, 030209 endocrinology & metabolism, Biology, MESH: Aldosterone Synthase, 03 medical and health sciences, MESH: In Situ Hybridization, MESH : Hyperplasia, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Hyperaldosteronism, Internal Medicine, medicine, Cytochrome P-450 CYP11B2, Humans, MESH : Middle Aged, Steroid 11-beta-hydroxylase, 030304 developmental biology, MESH : Aldosterone Synthase, MESH: Adenoma, MESH: Humans, MESH : Aldosterone, MESH: Hyperplasia, MESH : Humans, MESH: Aldosterone, MESH: Immunohistochemistry, MESH: Adult, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, Endocrinology, MESH : Adenoma, chemistry, Mineralocorticoid, Zona glomerulosa, Adrenal Cortex, Steroid 11-beta-Hydroxylase, MESH: Adrenal Cortex, MESH : Zona Glomerulosa, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Steroid 11-beta-Hydroxylase
Abstract

International audience; Primary aldosteronism is the most common form of secondary hypertension with hypokalemia and suppressed renin-angiotensin system caused by autonomous aldosterone production. Our aim was to compare zona glomerulosa (ZG) structure and function between control adrenals and the peritumoral tissue from patients operated on for aldosterone-producing adenoma. ZG morphology and CYP11B1, CYP11B2, and disabled 2 expression were studied in 15 control adrenals and 25 adrenals with aldosterone-producing adenoma. A transcriptome analysis was done using publicly available data sets. In control adrenals, ZG was discontinuous, and CYP11B2 expression was focal or partly continuous and localized to 3 structures, foci, megafoci, and aldosterone-producing cell clusters. CYP11B2 expression was restricted to a limited number of ZG cells expressing Dab2 but not CYP11B1; aldosterone-producing cell clusters were composed of cells with an intermediate phenotype expressing CYP11B2 but not disabled 2 or CYP11B1. In peritumoral tissue, large remodeling of the adrenal cortex was observed with increased nodulation and decreased vascularization that were not correlated with CYP11B2 expression. In 17 out of 25 adrenals, hyperplasia of adjacent ZG was observed with persistent expression of CYP11B2 that was extended to the entire ZG. In all of the adrenals from patients with aldosterone-producing adenoma, CYP11B2 expression was present in foci, megafoci, and aldosterone-producing cell clusters. Transcriptome profiling indicates a close relationship between peritumoral and control adrenal cortex. In conclusion, adrenal cortex remodeling, reduced vascularization, and ZG hyperplasia are major features of adrenals with aldosterone-producing adenoma. Transcriptional phenotyping is not in favor of this being an intermediate step toward the formation of aldosterone-producing adenoma.

Published
2010
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4. Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and HypertensionNovelty and Significance

Author

Martinez-Martinez, Ernesto, Calvier, Laurent, Fernández-Celis, Amaya, Rousseau, Elodie, Jurado-López, Raquel, Rossoni, Luciana, Jaisser, Frederic, Zannad, Faiez, Rossignol, Patrick, Cachofeiro, Victoria, López-Andrés, Natalia, Fundación Miguel Servet, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Universidade de Sao Paulo, Institute of Biomedical Sciences, Universidade de São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade de São Paulo = University of São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo = University of São Paulo (USP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
aldosterone, hypertension, MESH: Humans, MESH: Rats, fibrosis, MESH: Mineralocorticoid Receptor Antagonists, MESH: Rats, Wistar, galectin 3, MESH: Mice, Knockout, MESH: Galectin 3, MESH: Hypertension, MESH: Male, MESH: Hyperaldosteronism, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, inflammation, MESH: Mice, Inbred C57BL, MESH: Myocarditis, MESH: Fibroblasts, MESH: Spironolactone, MESH: Fibrosis, MESH: Animals, MESH: Disease Models, Animal, MESH: Mice, MESH: Rats, Inbred WKY, MESH: Cells, Cultured
Abstract

International audience; Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.

Published
2015
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5. Influence des critères diagnostiques sur l'interprétation du cathétérisme des veines surrénales dans l'hyperaldostéronisme primaire

Author

Lethielleux, Gaëlle, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Laurence Amar

Subjects
MESH: Hyperaldosteronism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Adrenal glands, Hyperaldostéronisme, MESH: Reproducibility of results, Cathétérisme veineux périphérique, Seuils diagnostiques, MESH: Peripheral venous catheterization, Diagnostic différentiel, Glandes surrénales, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Reproductibilité des résultats
Abstract

Guidelines promote the use of adrenal vein sampling (AVS) to document lateralized aldosterone hypersecretion in primary aldosteronism. However, there are large discrepancies between institutions in the criteria used to interpret its results. Our objective was to evaluate the consequences of these differences on the classification and management of patients. The results of all 537 AVS performed between 01/2001 and 06/2010 in our institution were interpreted with four diagnostic criteria used in experienced institutions where AVS is performed without cosyntropin (Brisbane, Padua, Paris, and Turin). AVS were classified as unsuccessful, lateralized, or not lateralized according to each set of criteria. AVS were classified as unsuccessful with the strictest criteria in 18% of cases versus 4% with the least strict criteria. With the least stringent criteria, 60% of AVS were classified as lateralized, versus 26% with the most stringent criteria. Multiple samples were available from at least one side for 155 AVS. These procedures were classified differently by at least two right-left sample pairs in 12% to 20% of cases. Thus, different sets of criteria used to interpret AVS in experienced institutions translate into extremely heterogeneous classifications, and hence management decisions, for patients with primary aldosteronism. AVS cannot be regarded as a gold standard until the most appropriate procedure and diagnostic criteria have been defined.; Les Recommandations promeuvent l'utilisation du cathétérisme des veines surrénales (KTVS) pour documenter la latéralisation de la sécrétion d'aldostérone dans l'hyperaldostéronisme primaire (HAP). Cependant, il existe de grandes disparités entre les centres experts concernant les critères utilisés pour interpréter ses résultats. Notre objectif était d'évaluer les conséquences de ces différences sur l'interprétation des KTVS et la prise en charge des patients. Les résultats de 537 KTVS réalisés entre 01/2001 et 06/2010 à l'Hôpital Européen Georges Pompidou ont été réinterprétés avec 4 critères diagnostiques utilisés dans des centres experts où le KTVS est réalisé sans ACTH (Brisbane, Padoue, Paris et Turin). Les KTVS étaient classés en non réussis, latéralisés ou non latéralisés, selon chaque ensemble de critères diagnostiques. Avec le critère de sélectivité le plus sévère, 18% des KTVS étaient classés comme non réussis, versus 4% avec le critère le plus permissif. Avec le critère de latéralisation le moins strict, 60% des KTVS étaient classés comme latéralisés, versus 26% avec le plus strict. Des échantillons multiples étaient disponibles au moins d'un côté pour 155 KTVS. Ces procédures étaient classées différemment par au moins deux paires de prélèvements droite-gauche dans 12 à 20% des cas. Ainsi, les différents critères utilisés dans les centres experts pour interpréter les KTVS ont pour conséquence une classification très hétérogène, et par conséquent une prise en charge différente des patients atteints d'HAP. Le KTVS ne peut pas être considéré comme un examen de référence, avant que la procédure et les critères diagnostiques les plus appropriés n'aient été définis.

Published
2015

6. Refractory hyperaldosteronism in heart failure is associated with plasma renin activity and angiotensinogen polymorphism

Author

Patrick Rossignol, Gian Franco Gensini, Andrea Ripoli, Michele Emdin, Cinzia Fatini, Rosanna Abbate, Elena Sticchi, Giuseppe Vergaro, Claudio Passino, Cristina Vassalle, Fondazione Toscana Gabriele Monasterio, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Institute of Clinical Physiology

Subjects
Aldosterone synthase, Male, MESH: Renin, Angiotensinogen, Plasma renin activity, Renin-Angiotensin System, chemistry.chemical_compound, Gene Frequency, MESH: Renin-Angiotensin System, Renin, Prospective Studies, MESH: Aged, Ejection fraction, Aldosterone, MESH: Middle Aged, biology, MESH: Genetic Predisposition to Disease, General Medicine, MESH: Follow-Up Studies, Middle Aged, Prognosis, Hyperaldosteronism, MESH: Hyperaldosteronism, Cardiology, Female, MESH: Cardiovascular Agents, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, MESH: Angiotensinogen, MESH: Prognosis, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Renin–angiotensin system, MESH: Polymorphism, Genetic, medicine, MESH: Gene Frequency, Humans, Genetic Predisposition to Disease, Aged, Heart Failure, Polymorphism, Genetic, MESH: Humans, business.industry, Cardiovascular Agents, medicine.disease, Angiotensin II, MESH: Male, MESH: Prospective Studies, chemistry, Heart failure, MESH: Heart Failure, biology.protein, MESH: Biomarkers, business, MESH: Female, Biomarkers, Follow-Up Studies
Abstract

International audience; AIMS:Refractory hyperaldosteronism is frequently observed in heart failure patients on up-to-date treatment, and holds prognostic value. Our aim was to identify which factors, either genetic or nongenetic, are associated with refractory hyperaldosteronism.METHODS:We enrolled 109 consecutive patients with left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 32 ± 10%; 86% males; age 65 ± 13 years (mean ± standard deviation)] on optimized adrenergic and renin-angiotensin-aldosterone system (RAAS) antagonism, undergoing clinical and neuroendocrine characterization, and genotyping for six polymorphisms in key RAAS-regulating genes [angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE-240A>T and I/D), angiotensin II type I receptor (AGTR1 1166A>C), aldosterone synthase (CYP11B2-344C>T) and renin (REN rs7539596)].RESULTS:Patients with refractory hyperaldosteronism (n = 41, 38%, with plasma concentration >180 ng/l, URL, median 283 ng/l, interquartile range 218-433), when compared with those without (106 ng/l, 74-144; P

Published
2015
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7. WNT/β-catenin signalling is activated in aldosterone-producing adenomas and controls aldosterone production

Author

Pierre Val, A. Berthon, Michelina Plateroti, Bruno Ragazzon, Laurence Amar, Antoine Martinez, Hervé Lefebvre, Maria-Christina Zennaro, Jérôme Bertherat, Seham Skah, Sheerazed Boulkroun, Guillaume Assié, Pierre-François Plouin, Isabelle Sahut-Barnola, M. Batisse-Lignier, Benoit Samson-Couterie, Coralie Drelon, Anne-Marie Lefrançois-Martinez, Frédérique Tissier, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Hypertension unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de médecine vasculaire et hypertension artérielle [CHU HEGP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Aldosterone synthase, Male, MESH: Adrenal Cortex Neoplasms, MESH: Mice, Knockout, MESH: Down-Regulation, chemistry.chemical_compound, Mice, MESH: Cytochrome P-450 CYP11B2, Nuclear Receptor Subfamily 4, Group A, Member 2, Nuclear Receptor Subfamily 4, Group A, Member 1, MESH: Nuclear Receptor Subfamily 4, Group A, Member 1, MESH: Animals, MESH: Nuclear Receptor Subfamily 4, Group A, Member 2, Aldosterone, Wnt Signaling Pathway, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Mice, Knockout, MESH: Middle Aged, Wnt signaling pathway, MESH: Wnt Signaling Pathway, LRP6, General Medicine, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, MESH: Hyperaldosteronism, Adrenocortical Adenoma, Female, MESH: Membrane Proteins, Signal transduction, MESH: Adrenocortical Adenoma, Adult, medicine.medical_specialty, Mice, 129 Strain, MESH: Cell Line, Tumor, Adenoma, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Mice, 129 Strain, MESH: Mice, Inbred C57BL, Internal medicine, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Renin–angiotensin system, Hyperaldosteronism, Genetics, medicine, Animals, Cytochrome P-450 CYP11B2, Humans, Molecular Biology, MESH: Mice, MESH: Humans, Membrane Proteins, MESH: Aldosterone, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Endocrinology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, chemistry, Zona glomerulosa, biology.protein, MESH: Female
Abstract

International audience; Primary aldosteronism (PA) is the main cause of secondary hypertension, resulting from adrenal aldosterone-producing adenomas (APA) or bilateral hyperplasia. Here, we show that constitutive activation of WNT/β-catenin signalling is the most frequent molecular alteration found in 70% of APA. We provide evidence that decreased expression of the WNT inhibitor SFRP2 may be contributing to deregulated WNT signalling and APA development in patients. This is supported by the demonstration that mice with genetic ablation of Sfrp2 have increased aldosterone production and ectopic differentiation of zona glomerulosa cells. We further show that β-catenin plays an essential role in the control of basal and Angiotensin II-induced aldosterone secretion, by activating AT1R, CYP21 and CYP11B2 transcription. This relies on both LEF/TCF-dependent activation of AT1R and CYP21 regulatory regions and indirect activation of CYP21 and CYP11B2 promoters, through increased expression of the nuclear receptors NURR1 and NUR77. Altogether, these data show that aberrant WNT/β-catenin activation is associated with APA development and suggest that WNT pathway may be a good therapeutic target in PA.

Published
2014
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8. Physiological partial aldosterone resistance in human newborns

Author

Martinerie, Laetitia, Pussard, Eric, Foix-L'Hélias, Laurence, Petit, François, Cosson, Claudine, Boileau, Pascal, Lombès, Marc, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie-hormonologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de Biochimie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Service d'Endocrinologie et Maladies de la reproduction

Subjects
MESH: Adolescent, MESH: Humans, MESH: Middle Aged, MESH: Renin, MESH: Infant, Newborn, MESH: Aldosterone, MESH: Adult, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Prospective Studies, MESH: Hyperaldosteronism, MESH: Mineralocorticoids, MESH: Renin-Angiotensin System, MESH: Young Adult, MESH: Potassium, MESH: Water-Electrolyte Balance, MESH: Sodium, MESH: Female
Abstract

International audience; In the neonatal period, the human kidney is characterized by an impaired ability to regulate water and sodium homeostasis, resembling partial aldosterone resistance. The aim of our study was to assess this hormonal insensitivity in newborn infants and to determine its relationship with neonatal sodium handling. We conducted a prospective study in 48 healthy newborns and their mothers. Aldosterone, renin, and electrolyte concentrations were measured in umbilical cords and in maternal plasma. Urinary aldosterone concentrations and sodium excretion were determined at urination within 24 h after birth. A significant difference was observed between aldosterone and renin levels in newborn infants compared with their mothers (817 +/- 73 versus 575 +/- 55 pg/mL and 79 +/- 10 versus 15 +/- 2 pg/mL, respectively, p < 0.001). This hyperactivation of the renin-angiotensin-aldosterone system was associated with hyponatremia and hyperkalemia in the newborn infants, and high urinary sodium loss, consistent with a partial aldosterone resistance at birth. Unlike plasma aldosterone, urinary aldosterone concentration was found highly correlated with plasma potassium concentrations, thus representing the best index for accurate evaluation of mineralocorticoid sensitivity. Our study represents a comprehensive characterization of the renin-aldosterone axis in newborn infants and provides evidence for physiologic partial aldosterone resistance in the neonatal period.

Published
2009
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9. Physiological partial aldosterone resistance in human newborns.: Aldosterone resistance at birth

Author

Claudine Cosson, Eric Pussard, Laetitia Martinerie, François Petit, Laurence Foix-L’Hélias, Pascal Boileau, Marc Lombès, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie-hormonologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de Biochimie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Service d'Endocrinologie et Maladies de la reproduction

Subjects
Hyperkalemia, MESH: Renin, Renin-Angiotensin System, chemistry.chemical_compound, 0302 clinical medicine, MESH: Renin-Angiotensin System, Renin, MESH: Sodium, Prospective Studies, Aldosterone, 0303 health sciences, MESH: Middle Aged, MESH: Infant, Newborn, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Water-Electrolyte Balance, Hyperaldosteronism, MESH: Hyperaldosteronism, MESH: Young Adult, Female, medicine.symptom, Hyponatremia, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Sodium, chemistry.chemical_element, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Young Adult, Internal medicine, Mineralocorticoids, Renin–angiotensin system, medicine, Humans, 030304 developmental biology, MESH: Adolescent, MESH: Humans, business.industry, Infant, Newborn, MESH: Aldosterone, MESH: Adult, medicine.disease, MESH: Prospective Studies, Endocrinology, chemistry, MESH: Mineralocorticoids, Mineralocorticoid, Pediatrics, Perinatology and Child Health, MESH: Potassium, MESH: Water-Electrolyte Balance, Potassium, business, MESH: Female, Homeostasis
Abstract

International audience; In the neonatal period, the human kidney is characterized by an impaired ability to regulate water and sodium homeostasis, resembling partial aldosterone resistance. The aim of our study was to assess this hormonal insensitivity in newborn infants and to determine its relationship with neonatal sodium handling. We conducted a prospective study in 48 healthy newborns and their mothers. Aldosterone, renin, and electrolyte concentrations were measured in umbilical cords and in maternal plasma. Urinary aldosterone concentrations and sodium excretion were determined at urination within 24 h after birth. A significant difference was observed between aldosterone and renin levels in newborn infants compared with their mothers (817 +/- 73 versus 575 +/- 55 pg/mL and 79 +/- 10 versus 15 +/- 2 pg/mL, respectively, p < 0.001). This hyperactivation of the renin-angiotensin-aldosterone system was associated with hyponatremia and hyperkalemia in the newborn infants, and high urinary sodium loss, consistent with a partial aldosterone resistance at birth. Unlike plasma aldosterone, urinary aldosterone concentration was found highly correlated with plasma potassium concentrations, thus representing the best index for accurate evaluation of mineralocorticoid sensitivity. Our study represents a comprehensive characterization of the renin-aldosterone axis in newborn infants and provides evidence for physiologic partial aldosterone resistance in the neonatal period.

Published
2009
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10. Physiological partial aldosterone resistance in human newborns

Author

Martinerie, Laetitia, Pussard, Eric, Foix-L'Hélias, Laurence, Petit, François, Cosson, Claudine, Boileau, Pascal, Lombès, Marc, Lombes, Marc, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie-hormonologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de Biochimie [Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Service d'Endocrinologie et Maladies de la reproduction

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Adolescent, MESH: Humans, MESH: Middle Aged, MESH: Renin, MESH: Infant, Newborn, MESH: Aldosterone, MESH: Adult, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Prospective Studies, MESH: Hyperaldosteronism, MESH: Mineralocorticoids, MESH: Renin-Angiotensin System, MESH: Young Adult, MESH: Potassium, MESH: Water-Electrolyte Balance, MESH: Sodium, MESH: Female
Abstract

International audience; In the neonatal period, the human kidney is characterized by an impaired ability to regulate water and sodium homeostasis, resembling partial aldosterone resistance. The aim of our study was to assess this hormonal insensitivity in newborn infants and to determine its relationship with neonatal sodium handling. We conducted a prospective study in 48 healthy newborns and their mothers. Aldosterone, renin, and electrolyte concentrations were measured in umbilical cords and in maternal plasma. Urinary aldosterone concentrations and sodium excretion were determined at urination within 24 h after birth. A significant difference was observed between aldosterone and renin levels in newborn infants compared with their mothers (817 +/- 73 versus 575 +/- 55 pg/mL and 79 +/- 10 versus 15 +/- 2 pg/mL, respectively, p < 0.001). This hyperactivation of the renin-angiotensin-aldosterone system was associated with hyponatremia and hyperkalemia in the newborn infants, and high urinary sodium loss, consistent with a partial aldosterone resistance at birth. Unlike plasma aldosterone, urinary aldosterone concentration was found highly correlated with plasma potassium concentrations, thus representing the best index for accurate evaluation of mineralocorticoid sensitivity. Our study represents a comprehensive characterization of the renin-aldosterone axis in newborn infants and provides evidence for physiologic partial aldosterone resistance in the neonatal period.

Published
2009
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11. Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis

Author

Frank Schweda, Dirk Heitzmann, Achim Weber, Markus Reichold, Celso E. Gomez-Sanchez, Stefan Jungbauer, Christina Sterner, Renaud Derand, Abeer El Wakil, Saïd Bendahhou, Raymond Mengual, Florian Lesage, Ines Tegtmeier, Nicolas Guy, Jacques Barhanin, Enzo Lalli, Richard Warth, Sascha Bandulik, M. Isabel Aller, William Wisden, Institute of Physiology, Universität Regensburg (UR), Clinic and Policlinic for Internal Medicine II, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Nice, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Division of Endocrinology, Montgomery Hospital, Instituto de Neurociencias de Alicante, Universidad Miguel Hernández [Elche] (UMH), Institute of Medical Sciences, University of Aberdeen, Department of Pathology, University hospital of Zurich [Zurich], and Deutsche Forschungsgemeinschaft, CNRS, European Section of Aldosterone Council

Subjects
Aldosterone synthase, Male, Familial hyperaldosteronism, MESH: Renin, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adrenal Glands, Renin, Homeostasis, MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Adrenal Glands, Aldosterone, Mice, Knockout, 0303 health sciences, biology, Adrenal gland, General Neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, MESH: Potassium Channels, Tandem Pore Domain, Hyperaldosteronism, 3. Good health, medicine.anatomical_structure, MESH: Hyperaldosteronism, MESH: Homeostasis, Female, medicine.medical_specialty, medicine.drug_class, 030209 endocrinology & metabolism, Nerve Tissue Proteins, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Potassium Channels, Tandem Pore Domain, MESH: Mice, Inbred C57BL, Internal medicine, Mineralocorticoids, medicine, Animals, Molecular Biology, MESH: Mice, 030304 developmental biology, General Immunology and Microbiology, MESH: Aldosterone, medicine.disease, MESH: Male, Mice, Inbred C57BL, Endocrinology, chemistry, MESH: Mineralocorticoids, Zona glomerulosa, Mineralocorticoid, MESH: Potassium, biology.protein, Potassium, MESH: Female
Abstract

TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute to the background conductance whose inhibition by angiotensin II stimulates aldosterone secretion. We used task1-/- mice to analyze the role of this channel in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism independent of salt intake, hypokalemia, and arterial 'low-renin' hypertension. The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase was absent in the outer cortex normally corresponding to the zona glomerulosa, but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid homeostasis and zonation were independent of the sex in young mice, but were restricted to females in adults. Patch-clamp experiments on adrenal cells suggest that task3 and other K+ channels compensate for the task1 absence. Adrenal zonation appears as a dynamic process that even can take place in adulthood. The striking changes in the adrenocortical architecture in task1-/- mice are the first demonstration of the causative role of a potassium channel in development/differentiation. ©2008 European Molecular Biology Organization., The study was supported by the Deutsche Forschungsgemeinschaft (SFB699 to RW), the Centre National de la Recherche scientifique (JB), and by the European Section of Aldosterone Council (11AD5B to JB).

Published
2008
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12. How Bartter’s and Gitelman’s Syndromes, and Dent’s Disease Have Provided Important Insights into the Function of Three Renal Chloride Channels: ClC-Ka/b and ClC-5

Author

Lourdel, Stéphane, Loffing, Johannes, Favre, Guillaume, Paulais, Marc, Nissant, Antoine, Fakitsas, Panos, Créminon, Christophe, Féraille, Eric, Verrey, François, Teulon, Jacques, Doucet, Alain, Deschênes, Georges, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique [AP-HP Hôpital Européen Georges Pompidou, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Interdisciplinaire Solidarités, Sociétés, Territoires (LISST), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Medicago Inc., Unité de Néphrologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, and Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-École des hautes études en sciences sociales (EHESS)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA)

Subjects
MESH: Rats, MESH: Probability, MESH: Biological Transport, MESH: Puromycin, [SDV]Life Sciences [q-bio], MESH: Rats, Sprague-Dawley, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Sodium Channels, MESH: Hypernatremia, Chloride Channels, MESH: Reverse Transcriptase Polymerase Chain Reaction, Animals, Humans, MESH: Animals, MESH: Epithelial Sodium Channels, MESH: Fluorescent Antibody Technique, MESH: Sodium-Potassium-Chloride Symporters, MESH: Immunoblotting, urogenital system, MESH: Reference Values, Bartter Syndrome, MESH: Sodium-Hydrogen Exchangers, MESH: Sensitivity and Specificity, MESH: Male, MESH: Hyperaldosteronism, MESH: Nephrosis, Kidney Diseases
Abstract

International audience; Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter's and Gitelman's, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory beta-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.

Published
2006
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13. A chloride channel at the basolateral membrane of the distal-convoluted tubule: a candidate ClC-K channel

Author

Paulais, Marc, Lourdel, Stéphane, Teulon, Jacques, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Rats, MESH: Sodium-Potassium-Chloride Symporters, MESH: Immunoblotting, urogenital system, MESH: Probability, MESH: Biological Transport, MESH: Puromycin, [SDV]Life Sciences [q-bio], MESH: Reference Values, MESH: Rats, Sprague-Dawley, MESH: Sodium-Hydrogen Exchangers, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Sensitivity and Specificity, MESH: Male, MESH: Sodium Channels, MESH: Hyperaldosteronism, MESH: Hypernatremia, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Nephrosis, MESH: Animals, MESH: Epithelial Sodium Channels, MESH: Fluorescent Antibody Technique
Abstract

International audience; Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter's and Gitelman's, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory beta-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.

Published
2006
Full Text
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14. A chloride channel at the basolateral membrane of the distal-convoluted tubule: a candidate ClC-K channel

Author

Lourdel, Stéphane, Paulais, Marc, Cluzeaud, Françoise, Bens, Marcelle, Tanemoto, Masayuki, Kurachi, Yoshihisa, Vandewalle, Alain, Teulon, Jacques, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
MESH: Rats, MESH: Sodium-Potassium-Chloride Symporters, MESH: Immunoblotting, urogenital system, MESH: Probability, MESH: Biological Transport, MESH: Puromycin, [SDV]Life Sciences [q-bio], MESH: Reference Values, MESH: Rats, Sprague-Dawley, MESH: Sodium-Hydrogen Exchangers, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Sensitivity and Specificity, MESH: Male, MESH: Sodium Channels, MESH: Hyperaldosteronism, MESH: Hypernatremia, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Nephrosis, MESH: Animals, MESH: Epithelial Sodium Channels, MESH: Fluorescent Antibody Technique
Abstract

International audience; Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter's and Gitelman's, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory beta-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.

Published
2006
Full Text
View/download PDF

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