Foetal lung maturation in 11β-hydroxysteroid dehydrogenase type 1 knockout mice

Sven Hundertmark, A. Dill, A. Ebert, B. Zimmermann, Y. V. Kotelevtsev, J. J. Mullins, J. R. Seckl

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42 Citations (Scopus)

Abstract

Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11β-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue). To test these data, we investigated 11β-HSD1 activity and lung maturity in the late foetal lung using 11β-HSD1 knockout mice. Control foetal mice showed high 11β-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11β-HSD1 -/- mice had lower surfactant protein-A (mRNA and protein) levels and significant depletion of lung surfactant according to both light and electron microscopy, and also had reduced amniotic fluid lecithin/sphingomyelin ratios. These results support the previous experiments with glycyrrhetinic acid and emphasize the importance of 11β-HSD1 in foetal lung maturation.

Original languageEnglish
Pages (from-to)545-549
Number of pages5
JournalHormone and Metabolic Research
Volume34
Issue number10
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

Keywords

  • 1.1.1.146
  • 11β-Hydroxysteroid Dehydrogenase
  • EC
  • Knockout Mice
  • Lung Maturation
  • Pulmonary Surfactant

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