Skip to main content
Log in

Effects of Glucocorticoids on Fetal and Neonatal Lung Development

  • Review Article
  • Published:
Treatments in Respiratory Medicine

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1

Similar content being viewed by others

References

  1. Liggins GC. Premature parturition after infusion of corticotrophin or Cortisol into foetal lambs. J Endocrinol 1968 Oct; 42(2): 323–9

    PubMed  CAS  Google Scholar 

  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): 515–25

    PubMed  CAS  Google Scholar 

  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, 2003

    Google Scholar 

  4. Halliday HL. Costs and benefits of perinatal corticosteroid treatment. Prenat Neonatal Med 2000; 5: 201–3

    Google Scholar 

  5. Baden M, Bauer CR, Colle E, et al. A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics 1972; 50: 526–34

    PubMed  CAS  Google Scholar 

  6. Mammel MC, Green TP, Johnson DE, et al. Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia. Lancet 1983 Jun 18; 8338: 1356–8

    Google Scholar 

  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): 106–11

    PubMed  CAS  Google Scholar 

  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, 2003

    Google Scholar 

  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, 2003

    Google Scholar 

  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, 2003

    Google Scholar 

  11. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond) 1998 Jun; 94(6): 557–72

    CAS  Google Scholar 

  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): F147–50

    PubMed  CAS  Google Scholar 

  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): R770–7

    PubMed  CAS  Google Scholar 

  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): L1142–8

    PubMed  CAS  Google Scholar 

  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): L665–72

    PubMed  CAS  Google Scholar 

  16. Fardy CH, Silverman M. Antioxidants in neonatal lung disease. Arch Dis Child Fetal Neonatal Ed 1995 Sep; 73(2): F112–7

    PubMed  CAS  Google Scholar 

  17. Adcock IM. Glucocorticoid-regulated transcription factors. Pulm Pharmacol Ther 2001; 14(3): 211–9

    PubMed  CAS  Google Scholar 

  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): 253–9

    PubMed  CAS  Google Scholar 

  19. Muller M, Renkawitz R. The glucocorticoid receptor. Biochim Biophys Acta 1991 Feb 16; 1088(2): 171–82

    PubMed  CAS  Google Scholar 

  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): 29–38

    PubMed  CAS  Google Scholar 

  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): 12940–6

    PubMed  CAS  Google Scholar 

  22. Wolffe AP. Transcriptional control: sinful repression. Nature 1997 May 1; 387(6628): 16–7

    PubMed  CAS  Google Scholar 

  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): 32312–21

    PubMed  CAS  Google Scholar 

  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): 1116–25

    PubMed  CAS  Google Scholar 

  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): 210–5

    PubMed  CAS  Google Scholar 

  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): 2992–9

    PubMed  CAS  Google Scholar 

  27. Jobe AH, Ikegami M. Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res 2001; 2(1): 27–32

    PubMed  CAS  Google Scholar 

  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): 782–8

    PubMed  CAS  Google Scholar 

  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: 771–83

    Google Scholar 

  30. DiFiore JW, Wilson JM. Lung development. Semin Pediatr Surg 1994; 3(4): 221–32

    PubMed  CAS  Google Scholar 

  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): 1297–305

    PubMed  CAS  Google Scholar 

  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): 4490–7

    PubMed  CAS  Google Scholar 

  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): 351–64

    PubMed  CAS  Google Scholar 

  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): 181–8

    PubMed  CAS  Google Scholar 

  35. Tschanz SA, Damke BM, Burri PH. Influence of postnatally administered glucocorticoids on rat lung growth. Biol Neonat 1995; 68(4): 229–45

    CAS  Google Scholar 

  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): 26–30

    PubMed  CAS  Google Scholar 

  37. Adamson IY, King GM. Postnatal development of rat lung following retarded fetal lung growth. Pediatr Pulmonol 1988; 4(4): 230–6

    PubMed  CAS  Google Scholar 

  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): 777–81

    PubMed  CAS  Google Scholar 

  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): 1158–63

    PubMed  CAS  Google Scholar 

  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): 235–40

    PubMed  CAS  Google Scholar 

  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): 606–13

    PubMed  CAS  Google Scholar 

  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): 7533–7

    PubMed  CAS  Google Scholar 

  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): 215–27

    PubMed  CAS  Google Scholar 

  44. Ross SA, McCaffery PJ, Drager UC, et al. Retinoids in embryonal development. Physiol Rev 2000 Jul; 80(3): 1021–54

    PubMed  CAS  Google Scholar 

  45. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 1995 Dec 15; 83(6): 835–9

    PubMed  CAS  Google Scholar 

  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): 705–9

    PubMed  CAS  Google Scholar 

  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): L305–10

    PubMed  CAS  Google Scholar 

  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): L955–60

    PubMed  CAS  Google Scholar 

  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): 357–68

    PubMed  Google Scholar 

  50. Jobe AJ. The new BPD: an arrest of lung development. Pediatr Res 1999 Dec; 46(6): 641–3

    PubMed  CAS  Google Scholar 

  51. Husain AN, Siddiqui NH, Stocker JT. Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia. Hum Pathol 1998 Jul; 29(7): 710–7

    PubMed  CAS  Google Scholar 

  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): 1333–46

    PubMed  CAS  Google Scholar 

  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): 945–58

    PubMed  CAS  Google Scholar 

  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): 872–81

    PubMed  CAS  Google Scholar 

  55. Abman SH. Bronchopulmonary dysplasia: “a vascular hypothesis”. Am J Respir Crit Care Med 2001 Nov 15; 164 (10 Pt 1): 1755–6

    PubMed  CAS  Google Scholar 

  56. Watterberg KL, Gerdes JS, Cook KL. Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatr Res 2001 Aug; 50(2): 190–5

    PubMed  CAS  Google Scholar 

  57. Wong YC, Beardsmore CS, Silverman M. Antenatal dexamethasone and subsequent lung growth. Arch Dis Child 1982 Jul; 57(7): 536–8

    PubMed  CAS  Google Scholar 

  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): 65–70

    PubMed  CAS  Google Scholar 

  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): 539–46

    PubMed  CAS  Google Scholar 

  60. Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992 Apr; 262 (4 Pt 1): L367–85

    PubMed  CAS  Google Scholar 

  61. Smith BT, Post M. Fibroblast-pneumonocyte factor. Am J Physiol 1989 Oct; 257 (4 Pt 1): L174–8

    PubMed  CAS  Google Scholar 

  62. Rooney SA, Young SL, Mendelson CR. Molecular and cellular processing of lung surfactant. FASEB J 1994 Sep; 8(12): 957–67

    PubMed  CAS  Google Scholar 

  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): L381–90

    PubMed  CAS  Google Scholar 

  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): L140–7

    PubMed  CAS  Google Scholar 

  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): L683–90

    PubMed  CAS  Google Scholar 

  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): 213–22

    PubMed  CAS  Google Scholar 

  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): 385–9

    PubMed  CAS  Google Scholar 

  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): L1048–57

    PubMed  CAS  Google Scholar 

  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): 1408–13

    PubMed  CAS  Google Scholar 

  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): 872–81

    PubMed  CAS  Google Scholar 

  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): 676–84

    PubMed  CAS  Google Scholar 

  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): L1–13

    PubMed  CAS  Google Scholar 

  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): 9096–100

    PubMed  CAS  Google Scholar 

  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): 1712–20

    PubMed  CAS  Google Scholar 

  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): L236–44

    PubMed  CAS  Google Scholar 

  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: 406–10

    PubMed  CAS  Google Scholar 

  77. Cole FS, Hamvas A, Nogee LM. Genetic disorders of neonatal respiratory function. Pediatr Res 2001 Aug; 50(2): 157–62

    PubMed  CAS  Google Scholar 

  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): 668–75

    PubMed  CAS  Google Scholar 

  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): 573–9

    PubMed  CAS  Google Scholar 

  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): 6531–6

    PubMed  CAS  Google Scholar 

  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): 1183–93

    PubMed  CAS  Google Scholar 

  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): 2166–73

    PubMed  CAS  Google Scholar 

  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): 781–6

    PubMed  CAS  Google Scholar 

  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): 121–30

    PubMed  CAS  Google Scholar 

  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): 907–13

    PubMed  CAS  Google Scholar 

  86. Matalon S, O’Brodovich H. Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance. Annu Rev Physiol 1999; 61: 627–61

    PubMed  CAS  Google Scholar 

  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): 8–10

    PubMed  Google Scholar 

  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): 345–55

    PubMed  Google Scholar 

  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): 325–8

    PubMed  CAS  Google Scholar 

  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): C491–6

    PubMed  Google Scholar 

  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): G1227–35

    PubMed  CAS  Google Scholar 

  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): F304–14

    PubMed  CAS  Google Scholar 

  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): C805–12

    PubMed  CAS  Google Scholar 

  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): C762–70

    PubMed  CAS  Google Scholar 

  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): C762–72

    PubMed  CAS  Google Scholar 

  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): 208–14

    PubMed  CAS  Google Scholar 

  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): L124–34

    PubMed  CAS  Google Scholar 

  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): 111–22

    PubMed  CAS  Google Scholar 

  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): 20702–11

    PubMed  CAS  Google Scholar 

  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): C1137–43

    PubMed  Google Scholar 

  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): L197–203

    PubMed  CAS  Google Scholar 

  102. Thibeault DW, Mabry S, Rezaiekhaligh M. Neonatal pulmonary oxygen toxicity in the rat and lung changes with aging. Pediatr Pulmonol 1990; 9(2): 96–108

    PubMed  CAS  Google Scholar 

  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): 1402–9

    PubMed  CAS  Google Scholar 

  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): 79–82

    PubMed  CAS  Google Scholar 

  105. Frank L, Sosenko IR. Prenatal development of lung antioxidant enzymes in four species. J Pediatr 1987 Jan; 110(1): 106–10

    PubMed  CAS  Google Scholar 

  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): 687–91

    PubMed  CAS  Google Scholar 

  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): 942–9

    PubMed  CAS  Google Scholar 

  108. Frank L. Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high O2 exposure. Pediatr Res 1992 Aug; 32(2): 215–21

    PubMed  CAS  Google Scholar 

  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): 409–16

    PubMed  CAS  Google Scholar 

  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): 569–74

    PubMed  CAS  Google Scholar 

  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): L187–91

    PubMed  CAS  Google Scholar 

  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): 273–8

    PubMed  CAS  Google Scholar 

  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): 143–51

    PubMed  Google Scholar 

  114. Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study [online]. Pediatrics 1998; 101: e7

    PubMed  CAS  Google Scholar 

  115. Grier DG, Halliday HL. Corticosteroids in the prevention and management of bronchopulmonary dysplasia. Semin Neonatol 2003 Feb; 8(1): 83–91

    PubMed  Google Scholar 

  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): 157–67

    PubMed  CAS  Google Scholar 

  117. Edwards HE, Burnham WM. The impact of corticosteroids on the developing animal. Pediatr Res 2001 Oct; 50(4): 433–40

    PubMed  CAS  Google Scholar 

  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): 515–23

    PubMed  CAS  Google Scholar 

  119. Matthews SG. Antenatal glucocorticoids and programming of the developing CNS. Pediatr Res 2000 Mar; 47(3): 291–300

    PubMed  CAS  Google Scholar 

  120. Jobe AH. Glucocorticoids in perinatal medicine: misguided rockets? J Pediatr 2000; 137: 1–3

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the assistance of Mrs Samantha Jameson in preparation of this manuscript. Dr Grier is supported by a grant from the Research and Development Office of the Department of Health and Personal Social Services, Northern Ireland. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David G. Grier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grier, D.G., Halliday, H.L. Effects of Glucocorticoids on Fetal and Neonatal Lung Development. Treat Respir Med 3, 295–306 (2004). https://doi.org/10.2165/00151829-200403050-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00151829-200403050-00004

Keywords

Navigation