Treatments in Respiratory Medicine

, Volume 3, Issue 5, pp 295–306

Effects of Glucocorticoids on Fetal and Neonatal Lung Development

Review Article

Abstract

Antenatal glucocorticoids have been used for 30 years to induce maturation of preterm fetal lungs. Stimulation of the pulmonary surfactant system has been regarded as the most important effect of antenatal glucocorticoids; however, as these drugs alter the expression of a large number of genes they affect the maturation of the lung in several other ways. Antioxidant enzyme production, lung fluid absorption and alveolar development are all affected by glucocorticoids administered in the perinatal period. There is evidence that glucocorticoids induce genes associated with the synthesis of surfactant proteins, fatty acid synthase, the epithelial sodium channel and the membrane protein sodium/potassium ATPase as well as several antioxidant enzymes including catalase, glutathione peroxidase and two superoxide dismutases. Glucocorticoids also increase the expression of vascular endothelial growth factor, which may inhibit alveolarization and lead to abnormally large alveoli. The use of both antenatal and postnatal glucocorticoids has increased in the past decade. However, as concerns about possible long-term effects have arisen, the mechanisms of how glucocorticoids alter the structure and function of the lungs needs to be determined to allow the development of more specific agents in the treatment of respiratory distress syndrome.

References

  1. 1.
    Liggins GC. Premature parturition after infusion of corticotrophin or Cortisol into foetal lambs. J Endocrinol 1968 Oct; 42(2): 323–9PubMedGoogle Scholar
  2. 2.
    Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972 Oct; 50(4): 515–25PubMedGoogle Scholar
  3. 3.
    Crowley P. Prophylactic corticosteroids for preterm birth (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003Google Scholar
  4. 4.
    Halliday HL. Costs and benefits of perinatal corticosteroid treatment. Prenat Neonatal Med 2000; 5: 201–3Google Scholar
  5. 5.
    Baden M, Bauer CR, Colle E, et al. A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics 1972; 50: 526–34PubMedGoogle Scholar
  6. 6.
    Mammel MC, Green TP, Johnson DE, et al. Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia. Lancet 1983 Jun 18; 8338: 1356–8Google Scholar
  7. 7.
    Avery GB, Fletcher AB, Kaplan M, et al. Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia. Pediatrics 1985 Jan; 75(1): 106–11PubMedGoogle Scholar
  8. 8.
    Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003Google Scholar
  9. 9.
    Halliday HL, Ehrenkranz RA, Doyle LW. Moderately early (7–14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003Google Scholar
  10. 10.
    Halliday HL, Ehrenkranz RA, Doyle LW. Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003Google Scholar
  11. 11.
    Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond) 1998 Jun; 94(6): 557–72Google Scholar
  12. 12.
    Vyas J, Kotecha S. Effects of antenatal and postnatal corticosteroids on the preterm lung. Arch Dis Child Fetal Neonatal Ed 1997 Sep; 77(2): F147–50PubMedGoogle Scholar
  13. 13.
    Sullivan LC, Orgeig S. Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of embryonic chickens. Am J Physiol Regul Integr Comp Physiol 2001 Sep; 281(3): R770–7PubMedGoogle Scholar
  14. 14.
    Tan RC, Ikegami M, Jobe AH, et al. Developmental and glucocorticoid regulation of surfactant protein mRNAs in preterm lambs. Am J Physiol 1999 Dec; 277 (6 Pt 1): L1142–8PubMedGoogle Scholar
  15. 15.
    Ingbar DH, Duvick S, Savick SK, et al. Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with dexamethasone. Am J Physiol 1997 Apr; 272 (4 Pt 1): L665–72PubMedGoogle Scholar
  16. 16.
    Fardy CH, Silverman M. Antioxidants in neonatal lung disease. Arch Dis Child Fetal Neonatal Ed 1995 Sep; 73(2): F112–7PubMedGoogle Scholar
  17. 17.
    Adcock IM. Glucocorticoid-regulated transcription factors. Pulm Pharmacol Ther 2001; 14(3): 211–9PubMedGoogle Scholar
  18. 18.
    Kellendonk C, Tronche F, Reichardt HM, et al. Mutagenesis of the glucocorticoid receptor in mice. J Steroid Biochem Mol Biol 1999 Apr–Jun; 69(1–6): 253–9PubMedGoogle Scholar
  19. 19.
    Muller M, Renkawitz R. The glucocorticoid receptor. Biochim Biophys Acta 1991 Feb 16; 1088(2): 171–82PubMedGoogle Scholar
  20. 20.
    Jantzen HM, Strahle U, Gloss B, et al. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell 1987 Apr 10; 49(1): 29–38PubMedGoogle Scholar
  21. 21.
    Ray A, Prefontaine KE, Ray P. Down-modulation of interleukin-6 gene expression by 17 beta-estradiol in the absence of high affinity DNA binding by the estrogen receptor. J Biol Chem 1994 Apr 29; 269(17): 12940–6PubMedGoogle Scholar
  22. 22.
    Wolffe AP. Transcriptional control: sinful repression. Nature 1997 May 1; 387(6628): 16–7PubMedGoogle Scholar
  23. 23.
    Newton R, Seybold J, Kuitert LM, et al. Repression of cyclooxygenase-2 and prostaglandin E2 release by dexamethasone occurs by transcriptional and posttranscriptional mechanisms involving loss of polyadenylated mRNA. J Biol Chem 1998 Nov 27; 273(48): 32312–21PubMedGoogle Scholar
  24. 24.
    Jobe AH, Newnham J, Willet K, et al. Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids. Pediatrics 1998 Nov; 102(5): 1116–25PubMedGoogle Scholar
  25. 25.
    Watterberg KL, Demers LM, Scott SM, et al. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996 Feb; 97(2): 210–5PubMedGoogle Scholar
  26. 26.
    Bry K, Lappalainen U, Hallman M. Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth. J Clin Invest 1997 Jun 15; 99(12): 2992–9PubMedGoogle Scholar
  27. 27.
    Jobe AH, Ikegami M. Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res 2001; 2(1): 27–32PubMedGoogle Scholar
  28. 28.
    Willet KE, Jobe AH, Ikegami M, et al. Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs. Pediatr Res 2000 Dec; 48(6): 782–8PubMedGoogle Scholar
  29. 29.
    Hodson WA. Normal and abnormal structural development of the lung. In: Polin RA, Fox WW, editors. Fetal and neonatal physiology. Philadelphia (PA): WB Saunders Company, 1992: 771–83Google Scholar
  30. 30.
    DiFiore JW, Wilson JM. Lung development. Semin Pediatr Surg 1994; 3(4): 221–32PubMedGoogle Scholar
  31. 31.
    Massaro D, Teich N, Maxwell S, et al. Postnatal development of alveoli: regulation and evidence for a critical period in rats. J Clin Invest 1985 Oct; 76(4): 1297–305PubMedGoogle Scholar
  32. 32.
    Condon J, Gosden C, Gardener D, et al. Expression of type 2 11-beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life. J Clin Endocrinol Metab 1998 Dec; 83(12): 4490–7PubMedGoogle Scholar
  33. 33.
    Beer DG, Butley MS, Cunha GR, et al. Autoradiographic localization of specific [3H]dexamethasone binding in fetal lung. Dev Biol 1984 Oct; 105(2): 351–64PubMedGoogle Scholar
  34. 34.
    Muglia LJ, Bae DS, Brown TT, et al. Proliferation and differentiation defects during lung development in corticotropin-releasing hormone-deficient mice. Am J Respir Cell Mol Biol 1999 Feb; 20(2): 181–8PubMedGoogle Scholar
  35. 35.
    Tschanz SA, Damke BM, Burri PH. Influence of postnatally administered glucocorticoids on rat lung growth. Biol Neonat 1995; 68(4): 229–45Google Scholar
  36. 36.
    Tschanz SA, Haenni B, Burri PH. Glucocorticoid induced impairment of lung structure assessed by digital image analysis. Eur J Pediatr 2002 Jan; 161(1): 26–30PubMedGoogle Scholar
  37. 37.
    Adamson IY, King GM. Postnatal development of rat lung following retarded fetal lung growth. Pediatr Pulmonol 1988; 4(4): 230–6PubMedGoogle Scholar
  38. 38.
    Okajima S, Matsuda T, Cho K, et al. Antenatal dexamethasone administration impairs normal postnatal lung growth in rats. Pediatr Res 2001 Jun; 49(6): 777–81PubMedGoogle Scholar
  39. 39.
    Pillow JJ, Hall GL, Willet KE, et al. Effects of gestation and antenatal steroid on airway and tissue mechanics in newborn lambs. Am J Respir Crit Care Med 2001 Apr; 163(5): 1158–63PubMedGoogle Scholar
  40. 40.
    Beck JC, Mitzner W, Johnson JW, et al. Betamethasone and the rhesus fetus: effect on lung morphometry and connective tissue. Pediatr Res 1981 Mar; 15(3): 235–40PubMedGoogle Scholar
  41. 41.
    Bhatt AJ, Amin SB, Chess PR, et al. Expression of vascular endothelial growth factor and Flk-1 in developing and glucocorticoid-treated mouse lung. Pediatr Res 2000 May; 47(5): 606–13PubMedGoogle Scholar
  42. 42.
    Quinn TP, Peters KG, De Vries C, et al. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A 1993 Aug 15; 90(16): 7533–7PubMedGoogle Scholar
  43. 43.
    Zeng X, Wert SE, Federici R, et al. VEGF enhances pulmonary vasculogenesis and disrupts lung morphogenesis in vivo. Dev Dyn 1998 Mar; 211(3): 215–27PubMedGoogle Scholar
  44. 44.
    Ross SA, McCaffery PJ, Drager UC, et al. Retinoids in embryonal development. Physiol Rev 2000 Jul; 80(3): 1021–54PubMedGoogle Scholar
  45. 45.
    Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 1995 Dec 15; 83(6): 835–9PubMedGoogle Scholar
  46. 46.
    Rush MG, Ul-Haq R, Chytil F. Opposing effects of retinoic acid and dexamethasone on cellular retinol-binding protein ribonucleic acid levels in the rat. Endocrinology 1991 Aug; 129(2): 705–9PubMedGoogle Scholar
  47. 47.
    Massaro GD, Massaro D. Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats. Am J Physiol 1996 Feb; 270 (2 Pt 1): L305–10PubMedGoogle Scholar
  48. 48.
    Massaro GD, Massaro D. Retinoic acid treatment partially rescues failed septation in rats and in mice. Am J Physiol Lung Cell Mol Physiol 2000 May; 278(5): L955–60PubMedGoogle Scholar
  49. 49.
    Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med 1967 Feb 16; 276(7): 357–68PubMedGoogle Scholar
  50. 50.
    Jobe AJ. The new BPD: an arrest of lung development. Pediatr Res 1999 Dec; 46(6): 641–3PubMedGoogle Scholar
  51. 51.
    Husain AN, Siddiqui NH, Stocker JT. Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia. Hum Pathol 1998 Jul; 29(7): 710–7PubMedGoogle Scholar
  52. 52.
    Coalson JJ, Winter VT, Siler-Khodr T, et al. Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 1999 Oct; 160(4): 1333–46PubMedGoogle Scholar
  53. 53.
    Albertine KH, Jones GP, Starcher BC, et al. Chronic lung injury in preterm lambs: disordered respiratory tract development. Am J Respir Crit Care Med 1999 Mar; 159(3): 945–58PubMedGoogle Scholar
  54. 54.
    Coalson JJ, Winter VT, Gerstmann DR, et al. Pathophysiologic, morphometric, and biochemical studies of the premature baboon with bronchopulmonary dysplasia. Am Rev Respir Dis 1992 Apr; 145 (4 Pt 1): 872–81PubMedGoogle Scholar
  55. 55.
    Abman SH. Bronchopulmonary dysplasia: “a vascular hypothesis”. Am J Respir Crit Care Med 2001 Nov 15; 164 (10 Pt 1): 1755–6PubMedGoogle Scholar
  56. 56.
    Watterberg KL, Gerdes JS, Cook KL. Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatr Res 2001 Aug; 50(2): 190–5PubMedGoogle Scholar
  57. 57.
    Wong YC, Beardsmore CS, Silverman M. Antenatal dexamethasone and subsequent lung growth. Arch Dis Child 1982 Jul; 57(7): 536–8PubMedGoogle Scholar
  58. 58.
    Smolders-de Haas H, Neuvel J, Schmand B, et al. Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up. Pediatrics 1990 Jul; 86(1): 65–70PubMedGoogle Scholar
  59. 59.
    Gluck L, Kulovich MV. Lecithin/spingomyelin ratios in amniotic fluid in normal and abnormal pregnancy. Am J Obstet Gynecol 1973 Feb 15; 115(4): 539–46PubMedGoogle Scholar
  60. 60.
    Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992 Apr; 262 (4 Pt 1): L367–85PubMedGoogle Scholar
  61. 61.
    Smith BT, Post M. Fibroblast-pneumonocyte factor. Am J Physiol 1989 Oct; 257 (4 Pt 1): L174–8PubMedGoogle Scholar
  62. 62.
    Rooney SA, Young SL, Mendelson CR. Molecular and cellular processing of lung surfactant. FASEB J 1994 Sep; 8(12): 957–67PubMedGoogle Scholar
  63. 63.
    Wagle S, Bui A, Ballard PL, et al. Hormonal regulation and cellular localization of fatty acid synthase in human fetal lung. Am J Physiol 1999 Aug; 277 (2 Pt 1): L381–90PubMedGoogle Scholar
  64. 64.
    Xu ZX, Stenzel W, Sasic SM, et al. Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung. Am J Physiol 1993 Aug; 265 (2 Pt 1): L140–7PubMedGoogle Scholar
  65. 65.
    Xu ZX, Viviano CJ, Rooney SA. Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid. Am J Physiol 1995 Apr; 268 (4 Pt 1): L683–90PubMedGoogle Scholar
  66. 66.
    Lu Z, Gu Y, Rooney SA. Transcriptional regulation of the lung fatty acid synthase gene by glucocorticoid, thyroid hormone and transforming growth factor-beta 1. Biochim Biophys Acta 2001 Jun 29; 1532(3): 213–22PubMedGoogle Scholar
  67. 67.
    Rooney SA, Smart DA, Weinhold PA, et al. Dexamethasone increases the activity but not the amount of choline-phosphate cytidylyltransferase in fetal rat lung. Biochim Biophys Acta 1990 Jun 14; 1044(3): 385–9PubMedGoogle Scholar
  68. 68.
    Ballard PL, Ning Y, Polk D, et al. Glucocorticoid regulation of surfactant components in immature lambs. Am J Physiol 1997 Nov; 273 (5 Pt 1): L1048–57PubMedGoogle Scholar
  69. 69.
    Ikegami M, Polk D, Jobe A. Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs. Am J Obstet Gynecol 1996 May; 174(5): 1408–13PubMedGoogle Scholar
  70. 70.
    Polk DH, Ikegami M, Jobe AH, et al. Postnatal lung function in preterm lambs: effects of a single exposure to betamethasone and thyroid hormones. Am J Obstet Gynecol 1995 Mar; 172(3): 872–81PubMedGoogle Scholar
  71. 71.
    Kari MA, Akino T, Hallman M. Prenatal dexamethasone and exogenous surfactant therapy: surface activity and surfactant components in airway specimens. Pediatr Res 1995 Nov; 38(5): 676–84PubMedGoogle Scholar
  72. 72.
    Mason RJ, Greene K, Voelker DR. Surfactant protein A and surfactant protein D in health and disease. Am J Physiol 1998 Jul; 275 (1 Pt 1): L1–13PubMedGoogle Scholar
  73. 73.
    Liley HG, White RT, Benson BJ, et al. Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung. Proc Natl Acad Sci U S A 1988 Dec; 85(23): 9096–100PubMedGoogle Scholar
  74. 74.
    Odom MJ, Snyder JM, Boggaram V, et al. Glucocorticoid regulation of the major surfactant associated protein (SP-A) and its messenger ribonucleic acid and of morphological development of human fetal lung in vitro. Endocrinology 1988 Oct; 123(4): 1712–20PubMedGoogle Scholar
  75. 75.
    Iannuzzi DM, Ertsey R, Ballard PL. Biphasic glucocorticoid regulation of pulmonary SP-A: characterization of inhibitory process. Am J Physiol 1993 Mar; 264 (3 Pt 1): L236–44PubMedGoogle Scholar
  76. 76.
    Nogee LM, de Mello DE, Dehner LP, et al. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993; 328: 406–10PubMedGoogle Scholar
  77. 77.
    Cole FS, Hamvas A, Nogee LM. Genetic disorders of neonatal respiratory function. Pediatr Res 2001 Aug; 50(2): 157–62PubMedGoogle Scholar
  78. 78.
    Beers MF, Shuman H, Liley HG, et al. Surfactant protein B in human fetal lung: developmental and glucocorticoid regulation. Pediatr Res 1995 Nov; 38(5): 668–75PubMedGoogle Scholar
  79. 79.
    Nogee LM, Dunbar III AE, Wert SE, et al. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001 Feb 22; 344(8): 573–9PubMedGoogle Scholar
  80. 80.
    Bruno MD, Bohinski RJ, Huelsman KM, et al. Lung cell-specific expression of the murine surfactant protein A (SP-A) gene is mediated by interactions between the SP-A promoter and thyroid transcription factor-1. J Biol Chem 1995 Mar 24; 270(12): 6531–6PubMedGoogle Scholar
  81. 81.
    Zhou L, Lim L, Costa RH, et al. Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. J Histochem Cytochem 1996 Oct; 44(10): 1183–93PubMedGoogle Scholar
  82. 82.
    Losada A, Tovar JA, Xia HM, et al. Down-regulation of thyroid transcription factor-1 gene expression in fetal lung hypoplasia is restored by glucocorticoids. Endocrinology 2000 Jun; 141(6): 2166–73PubMedGoogle Scholar
  83. 83.
    Dulkerian SJ, Gonzales LW, Ning Y, et al. Regulation of surfactant protein D in human fetal lung. Am J Respir Cell Mol Biol 1996 Dec; 15(6): 781–6PubMedGoogle Scholar
  84. 84.
    Rust K, Bingle L, Mariencheck W, et al. Characterization of the human surfactant protein D promoter: transcriptional regulation of SP-D gene expression by glucocorticoids. Am J Respir Cell Mol Biol 1996 Feb; 14(2): 121–30PubMedGoogle Scholar
  85. 85.
    Wang JY, Yeh TF, Lin YC, et al. Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome. Thorax 1996 Sep; 51(9): 907–13PubMedGoogle Scholar
  86. 86.
    Matalon S, O’Brodovich H. Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance. Annu Rev Physiol 1999; 61: 627–61PubMedGoogle Scholar
  87. 87.
    O’Brodovich H. Fetal lung liquid secretion: insights using the tools of inhibitors and genetic knock-out experiments. Am J Respir Cell Mol Biol 2001 Jul; 25(1): 8–10PubMedGoogle Scholar
  88. 88.
    O’Brodovich HM. Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome. Proc Assoc Am Physicians 1996 Sep; 108(5): 345–55PubMedGoogle Scholar
  89. 89.
    Hummler E, Barker P, Gatzy J, et al. Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice. Nat Genet 1996 Mar; 12(3): 325–8PubMedGoogle Scholar
  90. 90.
    O’Brodovich H, Canessa C, Ueda J, et al. Expression of the epithelial Na+ channel in the developing rat lung. Am J Physiol 1993 Aug; 265 (2 Pt 1): C491–6PubMedGoogle Scholar
  91. 91.
    Watanabe S, Matsushita K, Stokes JB, et al. Developmental regulation of epithelial sodium channel subunit mRNA expression in rat colon and lung. Am J Physiol 1998 Dec; 275 (6 Pt 1): G1227–35PubMedGoogle Scholar
  92. 92.
    Watanabe S, Matsushita K, McCray Jr PB, et al. Developmental expression of the epithelial Na+ channel in kidney and uroepithelia. Am J Physiol 1999 Feb; 276 (2 Pt 2): F304–14PubMedGoogle Scholar
  93. 93.
    Tchepichev S, Ueda J, Canessa C, et al. Lung epithelial Na channel subunits are differentially regulated during development and by steroids. Am J Physiol 1995 Sep; 269 (3 Pt 1): C805–12PubMedGoogle Scholar
  94. 94.
    Lazrak A, Samanta A, Venetsanou K, et al. Modification of biophysical properties of lung epithelial Na(+) channels by dexamethasone. Am J Physiol Cell Physiol 2000 Sep; 279(3): C762–70PubMedGoogle Scholar
  95. 95.
    Nakamura K, Stokes JB, McCray Jr PB. Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am J Physiol Cell Physiol 2002 Sep; 283(3): C762–72PubMedGoogle Scholar
  96. 96.
    Chow YH, Wang Y, Plumb J, et al. Hormonal regulation and genomic organization of the human amiloride-sensitive epithelial sodium channel alpha subunit gene. Pediatr Res 1999 Aug; 46(2): 208–14PubMedGoogle Scholar
  97. 97.
    Bremner HR, Freywald T, O’Brodovich HM, et al. Promoter analysis of the gene encoding the beta-subunit of the rat amiloride-sensitive epithelial sodium channel. Am J Physiol Lung Cell Mol Physiol 2002 Jan; 282(1): L124–34PubMedGoogle Scholar
  98. 98.
    Thomas CP, Auerbach SD, Zhang C, et al. The structure of the rat amiloride-sensitive epithelial sodium channel gamma subunit gene and functional analysis of its promoter. Gene 1999 Mar 4; 228(1–2): 111–22PubMedGoogle Scholar
  99. 99.
    Derfoul A, Robertson NM, Lingrel JB, et al. Regulation of the human Na/KATPase beta1 gene promoter by mineralocorticoid and glucocorticoid receptors. J Biol Chem 1998 Aug 14; 273(33): 20702–11PubMedGoogle Scholar
  100. 100.
    O’Brodovich H, Staub O, Rossier BC, et al. Ontogeny of alpha 1- and beta 1-isoforms of Na(+)-K(+)-ATPase in fetal distal rat lung epithelium. Am J Physiol 1993 May; 264 (5 Pt 1): C1137–43PubMedGoogle Scholar
  101. 101.
    Chalaka S, Ingbar DH, Sharma R, et al. Na(+)-K(+)-ATPase gene regulation by glucocorticoids in a fetal lung epithelial cell line. Am J Physiol 1999 Jul; 277 (1 Pt 1): L197–203PubMedGoogle Scholar
  102. 102.
    Thibeault DW, Mabry S, Rezaiekhaligh M. Neonatal pulmonary oxygen toxicity in the rat and lung changes with aging. Pediatr Pulmonol 1990; 9(2): 96–108PubMedGoogle Scholar
  103. 103.
    Holm BA, Notter RH, Siegle J, et al. Pulmonary physiological and surfactant changes during injury and recovery from hyperoxia. J Appl Physiol 1985 Nov; 59(5): 1402–9PubMedGoogle Scholar
  104. 104.
    Moison RM, Palinckx JJ, Roest M, et al. Induction of lipid peroxidation of pulmonary surfactant by plasma of preterm babies. Lancet 1993 Jan 9; 341(8837): 79–82PubMedGoogle Scholar
  105. 105.
    Frank L, Sosenko IR. Prenatal development of lung antioxidant enzymes in four species. J Pediatr 1987 Jan; 110(1): 106–10PubMedGoogle Scholar
  106. 106.
    Gerdin E, Tyden O, Eriksson UJ. The development of antioxidant enzymatic defence in the perinatal rat lung: activities of Superoxide dismutase, glutathione peroxidase, and catalase. Pediatr Res 1985 Jul; 19(7): 687–91PubMedGoogle Scholar
  107. 107.
    Asikainen TM, Raivio KO, Saksela M, et al. Expression and developmental profile of antioxidant enzymes in human lung and liver. Am J Respir Cell Mol Biol 1998 Dec; 19(6): 942–9PubMedGoogle Scholar
  108. 108.
    Frank L. Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure. Pediatr Res 1992 Aug; 32(2): 215–21PubMedGoogle Scholar
  109. 109.
    Chen Y, Martinez MA, Frank L. Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: a new rat model of pulmonary fibrosis (bronchopulmonary dysplasia). J Pediatr 1997 Mar; 130(3): 409–16PubMedGoogle Scholar
  110. 110.
    Frank L, Lewis PL, Sosenko IR. Dexamethasone stimulation of fetal rat lung antioxidant enzyme activity in parallel with surfactant stimulation. Pediatrics 1985 Mar; 75(3): 569–74PubMedGoogle Scholar
  111. 111.
    Walther FJ, David-Cu R, Mehta EI, et al. Higher lung antioxidant enzyme activity persists after single dose of corticosteroids in preterm lambs. Am J Physiol 1996 Aug; 271 (2 Pt 1): L187–91PubMedGoogle Scholar
  112. 112.
    Walther FJ, Jobe AH, Ikegami M. Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs of preterm lambs. J Appl Physiol 1998 Jul; 85(1): 273–8PubMedGoogle Scholar
  113. 113.
    Horbar JD, Badger GJ, Carpenter JH, et al. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 2002 Jul; 110 (1 Pt 1): 143–51PubMedGoogle Scholar
  114. 114.
    Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study [online]. Pediatrics 1998; 101: e7PubMedGoogle Scholar
  115. 115.
    Grier DG, Halliday HL. Corticosteroids in the prevention and management of bronchopulmonary dysplasia. Semin Neonatol 2003 Feb; 8(1): 83–91PubMedGoogle Scholar
  116. 116.
    Uno H, Lohmiller L, Thieme C, et al. Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques: I. Hippocampus. Brain Res Dev Brain Res 1990 May 1; 53(2): 157–67PubMedGoogle Scholar
  117. 117.
    Edwards HE, Burnham WM. The impact of corticosteroids on the developing animal. Pediatr Res 2001 Oct; 50(4): 433–40PubMedGoogle Scholar
  118. 118.
    Tsubota S, Adachi N, Chen J, et al. Dexamethasone changes brain monoamine metabolism and aggravates ischemic neuronal damage in rats. Anesthesiology 1999 Feb; 90(2): 515–23PubMedGoogle Scholar
  119. 119.
    Matthews SG. Antenatal glucocorticoids and programming of the developing CNS. Pediatr Res 2000 Mar; 47(3): 291–300PubMedGoogle Scholar
  120. 120.
    Jobe AH. Glucocorticoids in perinatal medicine: misguided rockets? J Pediatr 2000; 137: 1–3PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Child HealthQueen’s University BelfastNorthern Ireland, UK
  2. 2.Regional Neonatal UnitRoyal Maternity HospitalBelfastUK

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