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Horm Metab Res 2002; 34(10): 537-544
DOI: 10.1055/s-2002-35424
Original Basic
© Georg Thieme Verlag Stuttgart · New York

11β-Hydroxysteroid Dehydrogenase Type 1: A New Regulator of Fetal Lung Maturation

S.  Hundertmark 1 , A.  Dill 1 , H.  Bühler 2 , P.  Stevens 3 , K.  Looman 3 , V.  Ragosch 1 , J.  R.  Seckl 4 , C.  Lipka 1
  • 1Laboratory for Experimental Gynecology, Department of Obstetrics and Gynecology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany
  • 2Laboratory for Molecular Oncology, Department of Obstetrics and Gynecology, Marienhospital Herne, Universitätsklinik, Ruhr-Universität Bochum, Germany
  • 3Clinic of Neonatology, Charité Campus Mitte, Humboldt Universität Berlin, Germany
  • 4Molecular Medicine Centre, University of Edinburgh, UK
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Publikationsverlauf

Received: 11 December 2001

Accepted after revision: 25 July 2002

Publikationsdatum:
19. November 2002 (online)

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Abstract

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11β-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11β-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11β-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11β-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

Key words

11β-Hydroxysteroid Dehydrogenase - EC - 1.1.1.146 - Lung Maturation - Pulmonary Surfactant

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