Abstract
Infants of diabetic mothers are frequently hyperinsulinemic and have an increased incidence of neonatal respiratory distress syndrome, a disease caused by a deficiency in the production of pulmonary surfactant by alveolar type II cells. It has been hypothesized that insulin inhibits fetal lung type II cell differentiation. We have shown previously that insulin inhibits the accumulation of surfactant protein (SP)-A and SP-B mRNA and has no effect on SP-C mRNA levels in human fetal lung tissue maintained in vitro. We hypothesized that treatment with glucocorticoids, which are used clinically to accelerate human fetal lung maturation, would overcome the inhibitory effects of insulin on human fetal lung development. In the present study, human fetal lung explants were maintained in the presence or absence of Cortisol added alone, or in insulin plus Cortisol added together. Cortisol significantly decreased SP-A mRNA levels by approximately 50% at the 100 nM concentration and significantly increased levels by approximately 20% at the 1 nM concentration. Cortisol increased SP-B and SP-C mRNA levels in a dose-dependent fashion (5- and 45-fold at 100 nM Cortisol, respectively). The combination of 1 nM Cortisol and insulin resulted in inhibition of mRNA levels for SP-A, SP-B, and SP-C at the high insulin concentrations (approximately 50% inhibition for SP-A and SP-B and approximately 25% inhibition of SP-C mRNA levels, in the presence of 40 pmol/L × 10×3 insulin). Surprisingly, 100 nM Cortisol plus inhibitory concentrations of insulin increased SP-A mRNA levels (2-fold at 40 pmol/L × 10−3). SP-B and SP-C mRNA levels in the presence of 100 nM Cortisol plus insulin were generally unchanged when compared with levels in explants cultured in Cortisol alone. Thus, Cortisol modulates the inhibitory effects of insulin on SP mRNA levels in a dose-dependent manner.
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Dekowski, S., Snyder, J. The Combined Effects of Insulin and Cortisol on Surfactant Protein mRNA Levels. Pediatr Res 38, 513–521 (1995). https://doi.org/10.1203/00006450-199510000-00007
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DOI: https://doi.org/10.1203/00006450-199510000-00007