Lack of Renal 11 Beta-Hydroxysteroid Dehydrogenase type 2 at Birth, a Targeted Temporal Window for Neonatal Glucocorticoid Action in Human and Mice.: Lack of 11βHSD2 activity in newborn kidneys

Abstract : Background Glucocorticoid hormones play a major role in fetal organ maturation. Yet, excessive glucocorticoid exposure in utero can result in a variety of detrimental effects, such as growth retardation and increased susceptibility to the development of hypertension. To protect the fetus, maternal glucocorticoids are metabolized into inactive compounds by placental 11beta-hydroxysteroid dehydrogenase type2 (11βHSD2). This enzyme is also expressed in the kidney, where it prevents illicit occupation of the mineralocorticoid receptor by glucocorticoids. We investigated the role of renal 11βHSD2 in the control of neonatal glucocorticoid metabolism in the human and mouse. Methods Cortisol (F) and cortisone (E) concentrations were measured in maternal plasma, umbilical cord blood and human newborn urine using HPLC. 11βHSD2 activity was indirectly assessed by comparing the F/E ratio between maternal and neonatal plasma (placental activity) and between plasma and urine in newborns (renal activity). Direct measurement of renal 11βHSD2 activity was subsequently evaluated in mice at various developmental stages. Renal 11βHSD2 mRNA and protein expression were analyzed by quantitative RT-PCR and immunohistochemistry during the perinatal period in both species. Results We demonstrate that, at variance with placental 11βHSD2 activity, renal 11βHSD2 activity is weak in newborn human and mouse and correlates with low renal mRNA levels and absence of detectable 11βHSD2 protein. Conclusions We provide evidence for a weak or absent expression of neonatal renal 11βHSD2 that is conserved among species. This temporal and tissue-specific 11βHSD2 expression could represent a physiological window for glucocorticoid action yet may constitute an important predictive factor for adverse outcomes of glucocorticoid excess through fetal programming.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2012, 7 (2), pp.e31949. 〈10.1371/journal.pone.0031949〉
Liste complète des métadonnées

Littérature citée [50 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00661369
Contributeur : Marc Lombes <>
Soumis le : jeudi 19 janvier 2012 - 12:49:29
Dernière modification le : lundi 4 juin 2018 - 10:14:02
Document(s) archivé(s) le : vendredi 20 avril 2012 - 02:30:15

Fichier

journal.pone.0031949.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

USPC | UPMC | IRD

Citation

Laetitia Martinerie, Eric Pussard, Geri Meduri, Anne-Lise Delezoïde, Pascal Boileau, et al.. Lack of Renal 11 Beta-Hydroxysteroid Dehydrogenase type 2 at Birth, a Targeted Temporal Window for Neonatal Glucocorticoid Action in Human and Mice.: Lack of 11βHSD2 activity in newborn kidneys. PLoS ONE, Public Library of Science, 2012, 7 (2), pp.e31949. 〈10.1371/journal.pone.0031949〉. 〈inserm-00661369〉

Partager

Métriques

Consultations de la notice

154

Téléchargements de fichiers

158