Abstract
Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11β-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 11β-HSD1 activity and lung maturity in the late foetal lung using 11β-HSD1 knockout mice. Control foetal mice showed high 11β-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11β-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 11β-HSD1 in foetal lung maturation.
Key words
1.1.1.146 - 11β-Hydroxysteroid Dehydrogenase - EC - Lung Maturation - Pulmonary Surfactant - Knockout Mice
References
-
1
Hundertmark S, Dill A, Bühler H, Stevens P, Loomann K, Ragosch V, Seckl J R, Lipka C.
11β-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.
Horm Met Res.
2002;
34
537-544
-
2
Kotelevtsev Y, Holmes M C, Burchell A, Houston P M, Schmoll D, Jamieson P, Best R, Brown R, Edwards C R, Seckl J R, Mullins J J.
11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress.
Proc Natl Acad Sci USA.
1997;
94
14 924-14 929
-
3
Schoneshofer M, Weber B, Oelkers W, Nahoul K, Mantero F.
Urinary excretion rates of 15 free steroids: potential utility in differential diagnosis of Cushing's syndrome.
Clin Chem.
1986;
32
93-96
-
4
Wissel H, Looman A C, Fritzsche I, Rustow B, Stevens P A.
SP-A-binding protein BP55 is involved in surfactant endocytosis by type II pneumocytes.
Am J Physiol.
1996;
271
L432-L440
-
5
Bakewell W E, Viviano C J, Dixon D, Smith G J, Hook G E.
Confocal laser scanning immunofluorescence microscopy of lamellar bodies and pulmonary surfactant protein A in isolated alveolar type II cells.
Lab Invest.
1991;
65
87-95
-
6
Gluck L, Kulovich M V, Borer R C, Brenner P H, Anderson G G, Spellacy W N.
Diagnosis of the respiratory distress syndrome by amniocentesis.
Am J Obstet Gynecol.
1971;
173
629-635
-
7
Ragosch V, Jurgens S, Lorenz U, Stolowsky C, Arabin B, Weitzel H K.
Prediction of RDS by amniotic fluid analysis: a comparison of the prognostic value of traditional and recent methods.
J Perinat Med.
1992;
20
351-360
-
8
Hundertmark S, Buhler H, Ragosch V, Dinkelborg L, Arabin B, Weitzel H K.
Correlation of surfactant phosphatidylcholine synthesis and 11 beta-hydroxysteroid dehydrogenase in the foetal lung.
Endocrinology.
1995;
136
2573-2578
-
9
Tye L M, Burton A F.
Variation in the pattern of metabolism of corticosteroids in foetal mouse tissues.
Life Sci.
1980;
26
35-39
-
10
Abramovitz M, Carriero R, Murphy B E.
Investigation of factors influencing 11 beta-hydroxysteroid dehydrogenase (EC 1.1.1.146) activity in midgestational human foetal lung monolayer and explant cultures.
J Steroid Biochem.
1984;
21
677-683
-
11
Rajan V, Chapman K E, Lyons V, Jamieson P, Mullins J J, Edwards C R, Seckl J R.
Cloning, sequencing and tissue-distribution of mouse 11 beta-hydroxysteroid dehydrogenase-1 cDNA.
J Steroid Biochem Mol Biol.
1995;
52
141-147
-
12
Mantovani A, Ricciardi C, Stazi A V, Macri C, Piccioni A, Badellino E, De Vincenzi M, Caiola S, Patriarca M.
Teratogenicity study of ammonium glycyrrhizinate in the Sprague-Dawley rat.
Food Chem Toxicol.
1988;
26
435-440
-
13
Nicholas T E, Lugg M A.
The physiological significance of 11 beta-hydroxysteroid dehydrogenase in the rat lung.
J Steroid Biochem.
1982;
17
113-118
-
14
Zimmermann B.
Lung organoid culture.
Differentiation.
1987;
36
86-109
PD Dr. S. Hundertmark
Allgemeines Krankenhaus Altona
Paul-Ehrlich-Straße 1 · 22763 Hamburg · Germany
Phone: + 49 (30) 84 45 25 93
Fax: + 49 (30) 84 45 44 77
Email: sven.hundertmark@ak-altona.lbk-hh.de