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

S. Hundertmark; A. Dill; H. Bühler; P. Stevens; K. Looman; V. Ragosch; J. R. Seckl; C. Lipka

doi:10.1055/s-2002-35424

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2002; 34(10): 537-544
DOI: 10.1055/s-2002-35424

Original Basic

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

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

Full Text

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