Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates.: MR and renal maturation
| Autor: | Sophie Prevot, Anne-Lise Delezoide, Say Viengchareun, Marc Lombès, Francis Jaubert, Laetitia Martinerie, Pascal Boileau, Martine Sinico, Geri Meduri |
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| Přispěvatelé: | 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 Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'AnatomoPathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Service d'Anatomie et de Cytologie Pathologiques [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Antoine-Béclère, Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'endocrinologie, Service d'Endocrinologie et Maladies de la reproduction, This work was supported by funds from Inserm, University Paris-Sud 11 (BQR) and the European Section of Aldosterone Council (ESAC). Fellowships (to LM) were from the Association des Juniors en Pédiatrie, the Société Française d'Endocrinologie et Diabétologie Pédiatrique, Gallia and Pfizer Laboratories, France, and the Fonds d'Etudes et de Recherche du Corps Médical des hôpitaux de Paris., Université Paris-Sud - Paris 11 (UP11) - IFR93 - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine-Béclère, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Epithelial sodium channel Receptors Vasopressin MESH: Renin MESH: Receptors Glucocorticoid Drug Resistance Kidney Renin-Angiotensin System Mice chemistry.chemical_compound 0302 clinical medicine Endocrinology Mineralocorticoid receptor MESH: Renin-Angiotensin System 11-beta-Hydroxysteroid Dehydrogenase Type 2 MESH: Receptors Mineralocorticoid Renin MESH: Animals [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 0303 health sciences Aldosterone MESH: Infant Newborn [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism medicine.anatomical_structure Aquaporin 2 MESH: 11-beta-Hydroxysteroid Dehydrogenase Type 2 MESH: Drug Resistance Female MESH: Receptors Vasopressin medicine.medical_specialty medicine.drug_class 030209 endocrinology & metabolism MESH: Epithelial Sodium Channel Biology Article 03 medical and health sciences Receptors Glucocorticoid Internal medicine Renin–angiotensin system medicine Animals Humans Epithelial Sodium Channels MESH: Mice 030304 developmental biology mineralocorticoid receptor aldosterone MESH: Aquaporin 2 MESH: Humans renal development Infant Newborn MESH: Aldosterone MESH: Kidney MESH: Male Receptors Mineralocorticoid chemistry Mineralocorticoid MESH: Female Homeostasis |
| Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2009, 150 (9), pp.4414-24. ⟨10.1210/en.2008-1498⟩ Endocrinology, Endocrine Society, 2009, 150 (9), pp.4414-24. 〈10.1210/en.2008-1498〉 |
| ISSN: | 0013-7227 |
| DOI: | 10.1210/en.2008-1498⟩ |
| Popis: | International audience; The human neonatal period is characterized by renal immaturity with impaired capacity to regulate water and sodium homeostasis, resembling partial aldosterone resistance. Because aldosterone effects are mediated by the mineralocorticoid receptor (MR), we postulated that this hormonal unresponsiveness could be related to low MR expression in the distal nephron. We measured aldosterone and renin levels in umbilical cord blood of healthy newborns. We used quantitative real-time PCR and immunohistochemistry to analyze the expression of MR and key players of the mineralocorticoid signaling pathway during human and mouse renal development. High aldosterone and renin levels were found at birth. MR mRNA was detected in mouse kidney at d 16 postcoitum, peaking at d 18 postcoitum, but its expression was surprisingly very low at birth, rising progressively afterward. Similar biphasic temporal expression was observed during human renal embryogenesis, with a transient expression between 15 and 24 wk of gestation but an undetectable immunoreactive MR in late gestational and neonatal kidneys. This cyclic MR expression was tightly correlated with the evolution of the 11beta-hydroxysteroid dehydrogenase type 2 and the epithelial sodium channel alpha-subunit. In contrast, glucocorticoid and vasopressin receptors and aquaporin 2 followed a progressive and sustained evolution during renal maturation. Our study provides the first evidence for a low renal MR expression level at birth, despite high aldosterone levels, which could account for compromised postnatal sodium handling. Elucidation of regulatory mechanisms governing MR expression should lead to new strategies for the management of sodium waste in preterms and neonates. |
| Databáze: | OpenAIRE |
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