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Foetal lung maturation in 11beta-hydroxysteroid dehydrogenase type 1 knockout mice
S Hundertmark1, A Dill, A Ebert
1Laboratory for Experimental Gynaecology, Department of Obstetrics and Gynaecology, Clinic Benjamin Franklin, Free University Berlin, Germany. sven.hundertmark@ak-altona.lbk-hh.de
Summary
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is crucial for fetal lung maturation. Its absence in knockout mice led to impaired lung development and reduced surfactant, highlighting 11beta-HSD1's role in preventing respiratory distress syndrome.
Area of Science:
- Endocrinology
- Developmental Biology
- Pulmonary Medicine
Background:
- Glucocorticoids (GCs) are vital for fetal lung maturation and surfactant synthesis.
- Deficient GC action is a primary cause of respiratory distress syndrome (RDS).
- 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) amplifies intracellular GC activity by converting inactive cortisone to active cortisol.
Purpose of the Study:
- To investigate the role of 11beta-HSD1 in fetal lung maturation.
- To confirm findings from glycyrrhetinic acid-induced inhibition of 11beta-HSD1 in rats.
Main Methods:
- Utilized 11beta-HSD1 knockout (KO) mice to study fetal lung development.
- Assessed lung maturity through surfactant protein-A levels (mRNA and protein) and amniotic fluid lecithin/sphingomyelin ratios.
- Examined lung tissue using light and electron microscopy.
Main Results:
- 11beta-HSD1 KO mice exhibited significantly lower surfactant protein-A levels.
- Histological analysis revealed a depletion of lung surfactant in KO mice.
- Amniotic fluid lecithin/sphingomyelin ratios were reduced in the absence of 11beta-HSD1.
- Control mice showed high 11beta-HSD activity and plasma 11-dehydrocorticosterone.
Conclusions:
- Pulmonary 11beta-HSD1 activity is essential for normal fetal lung maturation.
- The enzyme plays a critical role in surfactant production and lung development.
- These findings underscore the importance of 11beta-HSD1 in preventing fetal lung immaturity and RDS.