Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates.

Laetitia Martinerie (1) , Say Viengchareun (1) , Anne-Lise Delezoïde (2) , Francis Jaubert (3) , Martine Sinico (4) , Sophie Prevot (5) , Pascal Boileau (6) , Géri Meduri (1, 7) , Marc Lombès (1, 8, 9)

1 Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
2 Service de Biologie du Développement
3 Service d'AnatomoPathologie
4 Service d'AnatomoPathologie
5 Service d'Anatomie et de Cytologie Pathologiques [Béclère]
6 Service de Pédiatrie et Réanimations néonatales [Béclère]
7 Service de génétique moléculaire, pharmacogénétique et hormonologie
8 Service d'endocrinologie
9 Service d'Endocrinologie et Maladies de la reproduction

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.

Mots clés: renal development; mineralocorticoid receptor; aldosterone; renal development.

Domaines: Endocrinologie et métabolisme

Laetitia Martinerie, Say Viengchareun, Anne-Lise Delezoïde, Francis Jaubert, Martine Sinico, et al.. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates.: MR and renal maturation.. Endocrinology, 2009, 150 (9), pp.4414-24. ⟨10.1210/en.2008-1498⟩. ⟨inserm-00385465⟩