11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.
Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-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 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-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 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.
Hundertmark
S
S
Laboratory for Experimental Gynecology, Department of Obstetrics and Gynecology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany. sven.hundertmark@ak-altona.lbk-hh.de
Dill
A
A
Bühler
H
H
Stevens
P
P
Looman
K
K
Ragosch
V
V
Seckl
J R
JR
Lipka
C
C
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 / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000196:embryology* / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D006034:Glycyrrhetinic Acid; D003345:Corticosterone