title: Changes in 11beta-hydroxysteroid dehydrogenase type 2 expression in a low-protein rat model of intrauterine growth restriction.
abstract: BACKGROUND
  Intrauterine growth restriction (IUGR) is associated with systemic hypertension of the offspring later in life. The exact mechanisms are still incompletely understood. 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) in the distal renal tubule protects the mineralocorticoid receptor from cortisol. As we did not find a suppression of 11β-HSD2 in total kidney of IUGR animals, our objective was to investigate whether a suppression of 11β-HSD2 could be detected on a more sophisticated level such as in situ protein and gene expression of 11β-HSD2 in mildly hypertensive IUGR offspring.
  
  
  METHODS
  IUGR rats after maternal low-protein diet (n = 17) were compared with controls (n = 18). At 70 and 120 days of age, in situ distribution of 11β-HSD2 gene and protein expression was investigated by RT-PCR of microdissected tubules and immunohistochemistry. For in situ localization studies, double staining for 11β-HSD2 and calbindin was used. Serum levels of corticosterone and dehydrocorticosterone were measured by tandem mass spectrometry.
  
  
  RESULTS
  In IUGR rats, intra-arterial blood pressure significantly increased at Day 120 of life. Serum corticosterone/dehydrocorticosterone ratios and 11β-HSD2 mRNA in total kidney were not altered in IUGR animals. However, 11β-HSD2 mRNA concentration was significantly lower in microdissected tubuli of IUGR animals (Day 120: 0.18 ± 0.14 vs 1.00 ± 0.32 rel. units in controls; P < 0.05). In IUGR animals, immunostaining scores for 11β-HSD2 were significantly lower than in controls (P < 0.05). Double staining with calbindin showed lower expression of 11β-HSD2 in distal segments of the distal tubule.
  
  
  CONCLUSIONS
  Our data indicate lower gene and protein expression of the pre-receptor enzyme 11β-HSD2 in IUGR animals when looking at specific renal compartments, but not in total kidney extracts. Thus, lower 11β-HSD2 as a mechanism for hypertension later in life might be missed without methods for in situ detection.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Ostreicher
authors.forename: Jorge Reis
authors.initials: JR
authors.lastname: Almeida
authors.forename: Valentina
authors.initials: V
authors.lastname: Campean
authors.forename: Manfred
authors.initials: M
authors.lastname: Rauh
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000031:analogs & derivatives / Q000097:blood; D018753:Diet, Protein-Restricted; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology*; D006973:Hypertension / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C003552:11-dehydrocorticosterone; D003345:Corticosterone