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Aldosterone postnatally, but not at birth, is required for optimal induction of renal mineralocorticoid receptor expression and sodium reabsorption.: Aldosterone regulation of renal MR expression

Abstract : Sodium wasting during the neonatal period is the consequence of a physiological aldosterone resistance, related to a low renal mineralocorticoid receptor (MR) expression at birth, both in humans and mice. To investigate whether aldosterone is involved in the neonatal regulation of MR expression, we compared aldosterone and corticosterone levels and renal MR expression by quantitative real-time PCR, between aldosterone synthase (AS) knockout, heterozygous, and wild type (WT) mice, at birth and postnatal d 8. Analysis of MR transcripts showed a similar expression profile in all genotypes, demonstrating that the lack of aldosterone does not modify either the low renal MR expression at birth or its postnatal induction. However, mRNA levels of the α-subunit of the epithelial sodium channel, a MR target gene, were significantly higher in WT compared with AS knockout mice, both at birth and postnatal d 8, despite high corticosterone levels in AS knockout mice, indicating that aldosterone is required for optimal renal induction of the epithelial sodium channel. Using organotypic cultures of newborn WT kidneys, we confirmed that aldosterone does not regulate MR expression at birth, but is instead capable of increasing MR expression in mature kidneys, unlike dexamethasone. In sum, we demonstrate both in vivo and in vitro, that, whereas aldosterone has no significant impact on renal MR expression at birth, it is crucial for optimal MR regulation in postnatal kidneys and for appropriate hydroelectrolytic balance. Understanding of MR-regulatory mechanisms could therefore lead to new therapeutic strategies for the management of sodium loss in preterms and neonates.
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https://www.hal.inserm.fr/inserm-00579433
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Submitted on : Thursday, April 7, 2011 - 2:21:41 PM
Last modification on : Friday, October 16, 2020 - 3:21:40 AM
Long-term archiving on: : Friday, July 8, 2011 - 2:31:47 AM

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Laetitia Martinerie, Say Viengchareun, Géri Meduri, Hyung-Suk Kim, James Luther, et al.. Aldosterone postnatally, but not at birth, is required for optimal induction of renal mineralocorticoid receptor expression and sodium reabsorption.: Aldosterone regulation of renal MR expression. Endocrinology, Endocrine Society, 2011, 152 (6), pp.2483-91. ⟨10.1210/en.2010-1460⟩. ⟨inserm-00579433⟩

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