title: Lack of renal 11 beta-hydroxysteroid dehydrogenase type 2 at birth, a targeted temporal window for neonatal glucocorticoid action in human and mice.
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.
authors.affiliation: INSERM, U693, Le Kremlin-Bicêtre, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Martinerie
authors.forename: Eric
authors.initials: E
authors.lastname: Pussard
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Pascal
authors.initials: P
authors.lastname: Boileau
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000032:analysis*; D000818:Animals; D000831:Animals, Newborn; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000201:enzymology*; D051379:Mice; D036801:Parturition; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2