Adenosine 3',5'-monophosphate analogs and β-adrenergic agonists induce the synthesis of the major surfactant apoprotein in human fetal lung in vitro

M. J. Odom, J. M. Snyder, C. R. Mendelson

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Abstract

The use of β-adrenergic agonists in the treatment of preterm labor has been found to be associated with a decreased incidence of respiratory distress syndrome (RDS) in premature newborns. β-Sympathomimetic agents, which activate adenylate cyclase and increase tissue cAMP levels, as well as cAMP analogs stimulate surfactant glycerophospholipid synthesis and secretion by fetal lung tissue. In the present study, we used antibodies directed against the major human pulmonary surfactant apoprotein, a 35,000-dalton glycoprotein, to evaluate the effects of the cAMP analog dibutyryl cAMP (Bt2cAMP) and the β-adrenergic agonist terbutaline on surfactant apoprotein synthesis in human fetal lung explants in organ culture. By use of immunoblot analysis, we found that Bt2cAMP (1 mM) markedly stimulated accumulation of the major surfactant apoprotein in human fetal lung explants, as did terbutaline. Bt2cAMP treatment also increased the relative rate of incoporation of [35S]methionine not the major surfactant apoprotein. The Bt2cAMP-induced increase in surfactant apoprotein synthesis and accumulation was associated with an increase in the levels of translatable surfactant apoprotein mRNA. Morphometric analysis at both the light and electron microscopic levels was used to evaluate the effects of Bt2cAMP on the morphology of the human fetal lung in vitro. After 48-h incubation with Bt2cAMP, the prealveolar ducts of the fetal lung explants were enlarged greatly, and the relative amount of interalveolar connective tissue was reduced compared to those in control tissues. The volume density of type II cells in the Bt2cAMP-treated explants was significantly greater than that in control explants at this time point; however, after 4 and 6 days of incubation, the volume density of type II cells in control and Bt2cAMP-treated tissues was similar, and the lumina of the prealveolar ducts of control tissues had a volume density similar to that of Bt2cAMP-treated explants. Bt2cAMP also had pronounced effects on the ultrastructural morphology of the human fetal lung explants. Large quantities of secreted lamellar bodies and tubular myelin were observed in the lumina of the prealveolar ducts of the Bt2cAMP-treated tissue. Few lamellar bodies and no tubular myelin were observed in the lamina of the prealveolar ducts of control tissues. These findings suggest that cAMP may serve an important regulatory role in the synthesis and secretion of the major surfactant apoprotein by human fetal lung.

Original languageEnglish (US)
Pages (from-to)1155-1163
Number of pages9
JournalEndocrinology
Volume121
Issue number3
StatePublished - 1987

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Adrenergic Agonists
Apoproteins
Surface-Active Agents
Adenosine
Lung
Terbutaline
Cell Count
Glycerophospholipids
Sympathomimetics
Premature Obstetric Labor
Organ Culture Techniques
In Vitro Techniques
Adenylyl Cyclases
Methionine
Connective Tissue
Glycoproteins
Fetus
Electrons
Light
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Adenosine 3',5'-monophosphate analogs and β-adrenergic agonists induce the synthesis of the major surfactant apoprotein in human fetal lung in vitro. / Odom, M. J.; Snyder, J. M.; Mendelson, C. R.

In: Endocrinology, Vol. 121, No. 3, 1987, p. 1155-1163.

Research output: Contribution to journalArticle

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