Foetal lung maturation in 11beta-hydroxysteroid dehydrogenase type 1 knockout mice.
Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11beta-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 11beta-HSD1 activity and lung maturity in the late foetal lung using 11beta-HSD1 knockout mice. Control foetal mice showed high 11beta-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11beta-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 11beta-HSD1 in foetal lung maturation.
Hundertmark
S
S
Laboratory for Experimental Gynaecology, Department of Obstetrics and Gynaecology, Clinic Benjamin Franklin, Free University Berlin, Germany. sven.hundertmark@ak-altona.lbk-hh.de
Dill
A
A
Ebert
A
A
Zimmermann
B
B
Kotelevtsev
Y V
YV
Mullins
J J
JJ
Seckl
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000097:blood; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D013109:Sphingomyelins / Q000378:metabolism
D010713:Phosphatidylcholines; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; D013109:Sphingomyelins; D007633:Keratins; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D006034:Glycyrrhetinic Acid; D003345:Corticosterone