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. 1974 Jun;53(6):1518–1526. doi: 10.1172/JCI107702

Evidence for Different Gestation-Dependent Effects of Cortisol on Cultured Fetal Lung Cells

Barry T Smith 1, John S Torday 1, C J P Giroud 1
PMCID: PMC302647  PMID: 4830219

Abstract

The effect of cortisol (5.5 μM) on primary monolayer cultures of trypsin-dispersed lung cells from rabbit fetuses of 20-28 days gestation was monitored with respect to (a) cellular growth as determined by DNA content after 72 h, at which time all cultures were in the exponential phase of growth, and (b) cellular maturation as reflected by the incorporation of [14C]-palmitate into saturated lecithin and its release into the culture medium.

Cortisol significantly increased growth in cultures prepared from 20 day (control: 59.8±8.9 nmol DNA/flask; cortisol: 118.7±15.7, P < 0.001) and 22 day (control: 69.2±17.2; cortisol: 106.7±13.3, P < 0.001) fetuses but had no effect on the growth of cells from 24 or 26 day fetuses. At 28 days, the effect was reversed, cortisol reducing growth by a factor of two (control: 42.0±8.5; cortisol: 19.3±4.0, P < 0.001).

Incorporation of palmitate into lecithin was expressed as picomoles incorporated per micromole DNA per flask, thus correcting for differences in the number of cells. Cortisol had no effect on palmitate incorporation until day 26, at which time it caused a slight increase (control: 51.2±5.5: cortisol: 72.8±16.2, P < 0.01) which became very striking by day 28 (control: 19.7±3.1; cortisol; 286.8±47.0, P < 0.001). The proportion of recovered radiolabeled lecithin that was disaturated rose with gestational age from 72% at 20 days to 98% at 28 days. Saturated lecithin made up over 90% at the two gestational ages (26 and 28 days) where cortisol increased palmitate incorporation. In contrast, cortisol had no effect on the incorporation of palmitate into sphingomyelin at any of the gestational ages studied.

The results suggest that cortisol may increase fetal pulmonary cellular growth in early gestation while enhancing maturation and slowing growth as term approaches.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVERY M. E., MEAD J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child. 1959 May;97(5 Pt 1):517–523. doi: 10.1001/archpedi.1959.02070010519001. [DOI] [PubMed] [Google Scholar]
  2. BUCKINGHAM S., AVERY M. E. Time of appearance of lung surfactant in the foetal mouse. Nature. 1962 Feb 17;193:688–689. doi: 10.1038/193688a0. [DOI] [PubMed] [Google Scholar]
  3. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baden M., Bauer C. R., Colle E., Klein G., Taeusch H. W., Jr, Stern L. A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics. 1972 Oct;50(4):526–534. [PubMed] [Google Scholar]
  5. Ballard P. L., Ballard R. A. Glucocorticoid receptors and the role of glucocorticoids in fetal lung development. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2668–2672. doi: 10.1073/pnas.69.9.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berliner D. L., Ruhmann A. G. Comparison of the growth of fibroblasts under the influence of 11-betahydroxy and 11-keto corticosteroids. Endocrinology. 1966 Feb;78(2):373–382. doi: 10.1210/endo-78-2-373. [DOI] [PubMed] [Google Scholar]
  7. Blank M. L., Nutter L. J., Privett O. S. Determination of the structure of lecithins. Lipids. 1966 Mar;1(2):132–135. doi: 10.1007/BF02533005. [DOI] [PubMed] [Google Scholar]
  8. CLEMENTS J. A. Surface phenomena in relation to pulmonary function. Physiologist. 1962 Feb;5:11–28. [PubMed] [Google Scholar]
  9. Carson S. H., Taeusch H. W., Jr, Avery M. E. Inhibition of lung cell division after hydrocortisone injection into fetal rabbits. J Appl Physiol. 1973 May;34(5):660–663. doi: 10.1152/jappl.1973.34.5.660. [DOI] [PubMed] [Google Scholar]
  10. DeLemos R. A., Shermeta D. W., Knelson J. H., Kotas R., Avery M. E. Acceleration of appearance of pulmonary surfactant in the fetal lamb by administration of corticosteroids. Am Rev Respir Dis. 1970 Sep;102(3):459–461. doi: 10.1164/arrd.1970.102.3.459. [DOI] [PubMed] [Google Scholar]
  11. Farrell P. M., Zachman R. D. Induction of choline phosphotransferase and lecithin synthesis in the fetal lung by corticosteroids. Science. 1973 Jan 19;179(4070):297–298. doi: 10.1126/science.179.4070.297. [DOI] [PubMed] [Google Scholar]
  12. Giannopoulos G. Glucocorticoid receptors in lung. I. Specific binding of glucocorticoids to cytoplasmic components of rabbit fetal lung. J Biol Chem. 1973 Jun 10;248(11):3876–3883. [PubMed] [Google Scholar]
  13. Giannopoulos G., Mulay S., Solomon S. Cortisol receptors in rabbit fetal lung. Biochem Biophys Res Commun. 1972 Apr 28;47(2):411–418. doi: 10.1016/0006-291x(72)90729-2. [DOI] [PubMed] [Google Scholar]
  14. Gluck L., Kulovich M. V., Brody S. J. Rapid quantitative measurement of lung tissue phospholipids. J Lipid Res. 1966 Jul;7(4):570–574. [PubMed] [Google Scholar]
  15. Gluck L., Motoyama E. K., Smits H. L., Kulovich M. V. The biochemical development of surface activity in mammalian lung. I. The surface-active phospholipids; the separation and distribution of surface-active lecithin in the lung of the developing rabbit fetus. Pediatr Res. 1967 Jul;1(4):237–246. doi: 10.1203/00006450-196707000-00001. [DOI] [PubMed] [Google Scholar]
  16. Goldenberg V. E., Buckingham S., Sommers S. C. Pilocarpine stimulation of granular pneumocyte secretion. Lab Invest. 1969 Feb;20(2):147–158. [PubMed] [Google Scholar]
  17. Goldenberg V. E., Buckingham S., Sommers S. C. Pulmonary alveolar lesions in vagotomized rats. Lab Invest. 1967 May;16(5):693–705. [PubMed] [Google Scholar]
  18. HAM R. G. An improved nutrient solution for diploid Chinese hamster and human cell lines. Exp Cell Res. 1963 Feb;29:515–526. doi: 10.1016/s0014-4827(63)80014-2. [DOI] [PubMed] [Google Scholar]
  19. Kikkawa Y., Motoyama E. K., Gluck L. Study of the lungs of fetal and newborn rabbits. Morphologic, biochemical, and surface physical development. Am J Pathol. 1968 Jan;52(1):177–210. [PMC free article] [PubMed] [Google Scholar]
  20. Klein G. P., De Levie M., Giroud C. J. Simultaneous measurement of plasma cortisol, cortisone, corticosterone, corticosterone sulfate and 11-deoxycorticosterone sulfate by competitive protein binding assays during the perinatal period. Steroids. 1972 Feb;19(2):275–291. doi: 10.1016/0039-128x(72)90011-6. [DOI] [PubMed] [Google Scholar]
  21. Kotas R. V., Avery M. E. Accelerated appearance of pulmonary surfactant in the fetal rabbit. J Appl Physiol. 1971 Mar;30(3):358–361. doi: 10.1152/jappl.1971.30.3.358. [DOI] [PubMed] [Google Scholar]
  22. Liggins G. C., Howie R. N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972 Oct;50(4):515–525. [PubMed] [Google Scholar]
  23. Morgan T. E. Biosynthesis of pulmonary surface-active lipid. Arch Intern Med. 1971 Mar;127(3):401–407. [PubMed] [Google Scholar]
  24. Motoyama E. K., Orzalesi M. M., Kikkawa Y., Kaibara M., Wu B., Zigas C. J., Cook C. D. Effect of cortisol on the maturation of fetal rabbit lungs. Pediatrics. 1971 Oct;48(4):547–555. [PubMed] [Google Scholar]
  25. STACHENKO J., LAPLANTE C., GIROUD C. J. DOUBLE ISOTOPE DERIVATIVE ASSAY OF ALDOSTERONE, CORTICOSTERONE, AND CORTISOL. Can J Biochem. 1964 Sep;42:1275–1291. doi: 10.1139/o64-137. [DOI] [PubMed] [Google Scholar]
  26. Smith B. T., Torday J. S., Giroud C. J. The growth promoting effect of cortisol on human fetal lung cells. Steroids. 1973 Oct;22(4):515–524. doi: 10.1016/0039-128x(73)90007-x. [DOI] [PubMed] [Google Scholar]
  27. Spellacy W. N., Buhi W. C., Riggall F. C., Holsinger K. L. Human amniotic fluid lecithin-sphingomyelin ratio changes with estrogen or glucocorticoid treatment. Am J Obstet Gynecol. 1973 Jan 15;115(2):216–218. doi: 10.1016/0002-9378(73)90288-3. [DOI] [PubMed] [Google Scholar]
  28. Taeusch H. W., Jr, Heitner M., Avery M. E. Accelerated lung maturation and increased survival in premature rabbits treated with hydrocortisone. Am Rev Respir Dis. 1972 Jun;105(6):971–973. doi: 10.1164/arrd.1972.105.6.971. [DOI] [PubMed] [Google Scholar]
  29. Tombropoulos E. G. Lipid synthesis by lung subcellular particles. Arch Intern Med. 1971 Mar;127(3):408–412. [PubMed] [Google Scholar]

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