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, Inhaltsverzeichnis

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

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References

1 Lorenz U, Jurgens S, Ragosch V, Kipper-Kreissl B, Weitzel H. Medical prevention of respiratory distress syndrome. Gynäkologe. 1991; 24 223-227
2 Ballard P L, Ballard R A. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol. 1995; 173 254-262
3 Liggins G C. Fetal lung maturation. Aust N Z J Obstet Gynaecol. 1994; 34 247-250
4 Rooney S A, Young S L, Mendelson C R. Molecular and cellular processing of lung surfactant. FASEB J. 1994; 8 957-967
5 Mendelson C R, Boggara V. Hormonal control of the surfactant system in fetal lung. Ann Rev Physol. 1991; 53 415-440
6 Gross I. Regulation of fetal lung maturation. Am J Physiol. 1990; 259 L337-344
7 Cole T J, Blendy J A, Monaghan A P, Krieglstein K, Schmid W, Aguzzi A, Fantuzzi G, Hummler E, Unsicker K, Schutz G. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 1995; 9 1608-1621
8 White P C, Mune T, Agarwal A K. 11 beta-hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr Rev. 1997; 18 135-156
9 Diaz R, Brown R W, Seckl J R. Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions. J Neurosci. 1998; 18 2570-2580
10 Jamieson P M, Chapman K E, Edwards C R, Seckl J R. 11 beta-hydroxysteroid dehydrogenase is an exclusive 11 beta-reductase in primary cultures of rat hepatocytes: effect of physicochemical and hormonal manipulations. Endocrinology. 1995; 136 4754-4761
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 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 fetal lung. Endocrinology. 1995; 136 2573-2578
13 Funder J W, Pearce P T, Smith R, Smith A I. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science. 1988; 242 583-585
14 Albiston A L, Obeyesekere V R, Smith R E, Krozowski Z S. Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol. 1994; 105 R11-17
15 Brown R W, Chapman K E, Kotelevtsev Y, Yau J L, Lindsay R S, Brett L, Leckie C, Murad P, Lyons V, Mullins J J, Edwards C R, Seckl J R. Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2. Biochem J. 1996; 313 1007-1017
16 Brown R W, Diaz R, Robson A C, Kotelevtsev Y V, Mullins J J, Kaufman M H, Seckl J R. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology. 1996; 137 794-797
17 Hundertmark S, Ragosch V, Schein B, Buhler H, Lorenz U, Fromm M, Weitzel H K. Gestational age dependence of 11 beta-hydroxysteroid dehydrogenase and its relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of fetal rat. Biochim Biophys Acta. 1994; 1210 348-354
18 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. 11-beta-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
19 Monder C, Stewart P M, Lakshmi V, Valentino R, Burt D, Edwards C R. Licorice inhibits corticosteroid 11 beta-dehydrogenase of rat kidney and liver: in vivo and in vitro studies. Endocrinology. 1989; 125 1046-1053
20 Lonka L, Smith R. How liquorice works. Lancet. 1987; 2 1206-1207
21 Stewart P M, Wallace A M, Valentino R, Burt D, Shackleton C H, Edwards C R. Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet. 1987; 2 821-824
22 Connelly I H, Hammond G L, Harding P G, Possmayer F. Levels of surfactant-associated protein messenger ribonucleic acids in rabbit lung during perinatal development and after hormonal treatment. Endocrinology. 1991; 129 2583-2591
23 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
24 Heilmann P, Heide J, Schoneshofer M. Determination of 18 beta-glycyrrhetinic acid in human serum using the fully automated ALCA-system. Eur J Clin Chem Clin Biochem. 1997; 35 539-543
25 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
26 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
27 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
28 Zimmermann B. Lung organoid culture. Differentiation. 1987; 36 86-109
29 Tadera J V. Control of lung differentiation in vitro. Dev Biol. 1967; 2 489-512
30 Zimmermann B. Influence of corticosteroids and thyroxine on lung development in vitro. Acta Endocrinol. 1985; 2 35-36
31 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 L432-440
32 Paine R, Ben-Ze’ev A, Farmer S R, Brody J S. The pattern of cytokeratin synthesis is a marker of type 2 cell differentiation in adult and maturing fetal lung alveolar cells. Dev Biol. 1988; 129 505-515
33 Endo H, Oka T. Histological and immunohistochemical analysis of lung development, with particular reference to lung hypoplasia. Early Hum Dev. 1995; 43 233-244
34 Sano K, Fisher J, Mason R J, Kuroki Y, Schilling J, Benson B, Voelker D. Isolation and sequence of a cDNA clone for the rat pulmonary surfactant-associated protein (PSP-A). Biochem Biophys Res Commun. 1987; 144 367-374
35 Korfhagen T R, Bruno M D, Glasser S W, Ciraolo P J, Whitsett J A, Lattier D L, Wikenheiser K A, Clark J C. Murine pulmonary surfactant SP-A gene: cloning, sequence, and transcriptional activity. Am J Physiol. 1992; 263 L546-554
36 Nudel U, Zakut R, Shani M, Neuman S, Levy Z, Yaffe D. The nucleotide sequence of the rat cytoplasmic beta-actin gene. Nucleic Acids Res. 1983; 11 1759-1771
37 Tye L M, Burton A F. Variation in the pattern of metabolism of corticosteroids in fetal mouse tissues. Life Sci. 1980; 26 35-39
38 Abramovitz M, Carriero R, Murphy B E. Investigation of factors influencing 11 beta-hydroxysteroid dehydrogenase (EC 1.1.1.146) activity in midgestational human fetal lung monolayer and explant cultures. J Steroid Biochem. 1984; 21 677-683
39 Lucier G W, Sonawane B R, McDaniel O S. Glucuronidation and deglucuronidation reactions in hepatic and extrahepatic tissues during perinatal development. Drug Metab Dispos. 1977; 5 279-287
40 Mantovani A, Ricciardi C, Stazi A V, Macri C, Piccioni A, Barellino E, de Vincenti M, Caiola S, Patriarca M. Teratogenicity study of ammonium glycyrrhizinate in the Sprague-Dawley rat. Food Chem Toxicol. 1988; 26 435-440
41 Edwards C R, Benediktsson R, Lindsay R S, Seckl J R. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension?. Lancet. 1993; 341 355-357
42 Benediktsson R, Calder A A, Edwards C R, Seckl J R. Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol. 1997; 46 161-166
43 Burton P J, Waddell B J. 11 beta-Hydroxysteroid dehydrogenase in the rat placenta: developmental changes and the effects of altered glucocorticoid exposure. J Endocrinol. 1994; 143 505-513
44 Barlow S M, Morrison P J, Sullivan F M. Plasma corticosterone levels during pregnancy in the mouse. Br J Pharmacol. 1973; 48 346P
45 Cohen A. Plasma corticosterone concentration in the foetal rat. Horm Metab Res. 1973; 5 66
46 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
47 Spinks E A, Fenwick G R. The determination of glycyrrhizin in selected UK liquorice products. Food Addit Contam. 1990; 7 769-778
48 Stormer F C, Reistad R, Alexander J. Glycyrrhizic acid in liquorice - evaluation of health hazard. Food Chem Toxicol. 1993; 31 303-312
49 Seckl J R. Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease. Steroids. 1997; 62 89-94

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