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The combined effects of insulin and cortisol on surfactant protein mRNA levels
1Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242, USA.
Insights
Glucocorticoids can counteract insulin's inhibitory effect on fetal lung development. This research explores how cortisol impacts surfactant protein mRNA levels in human fetal lung explants exposed to insulin.
Area of Science:
- Biochemistry
- Developmental Biology
- Neonatology
Background:
- Infants of diabetic mothers often experience hyperinsulinemia, increasing the risk of neonatal respiratory distress syndrome.
- Insulin is hypothesized to inhibit fetal lung type II cell differentiation, crucial for pulmonary surfactant production.
- Previous studies indicated insulin inhibits surfactant protein (SP)-A and SP-B mRNA accumulation in human fetal lung tissue.
Purpose of the Study:
- To investigate whether glucocorticoid treatment can overcome insulin's inhibitory effects on human fetal lung development.
- To determine the impact of cortisol on surfactant protein mRNA levels in the presence and absence of insulin.
Main Methods:
- Human fetal lung explants were cultured in vitro.
- Explants were treated with cortisol alone or in combination with insulin.
- Levels of SP-A, SP-B, and SP-C mRNA were quantified.
Main Results:
- Cortisol demonstrated a dose-dependent effect on SP-A mRNA, decreasing it at 100 nM and increasing it at 1 nM.
- Cortisol significantly increased SP-B and SP-C mRNA levels in a dose-dependent manner.
- At low cortisol concentrations (1 nM), insulin inhibited SP-A, SP-B, and SP-C mRNA levels.
- Surprisingly, high cortisol concentrations (100 nM) combined with insulin increased SP-A mRNA levels.
Conclusions:
- Glucocorticoids, particularly at higher concentrations, can overcome insulin's inhibitory effects on surfactant protein mRNA expression in fetal lung development.
- This suggests a potential therapeutic window for glucocorticoids in managing respiratory distress in infants of diabetic mothers.
- The complex interplay between insulin and cortisol in regulating lung maturation warrants further investigation.
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 x 10(-3) insulin). Surprisingly, 100 nM cortisol plus inhibitory concentrations of insulin increased SP-A mRNA levels (2-fold at 40 pmol/L x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)