Androgens delay human fetal lung maturation in vitro.

Area of Science:

• Biochemistry
• Developmental Biology
• Endocrinology

Background:

• Pulmonary surfactant, a lipid-protein complex, is crucial for preventing alveolar atelectasis in mature lungs.
• Prenatal surfactant production surges between 28-34 weeks gestation, triggered by glucocorticoids stimulating alveolar epithelial cells.
• Mesenchymal-epithelial interactions mediate glucocorticoid-induced surfactant synthesis.

Purpose of the Study:

• To investigate the role of fetal adrenal androgens in regulating human fetal lung development.
• To examine the effects of androgens and glucocorticoids on surfactant synthesis in vitro.
• To elucidate the mechanisms by which adrenal hormones influence lung maturation.

Main Methods:

• Culturing midgestation human fetal lung explants in serum-free medium.
• Assessing de novo saturated phosphatidylcholine (SPC) synthesis over time.
• Administering dexamethasone (DEX) and dihydrotestosterone (DHT) to culture media.
• Using flutamide to investigate androgen receptor involvement.

Main Results:

• Spontaneous increase in SPC synthesis observed on day 5 in culture.
• Dexamethasone (DEX) accelerated and enhanced SPC synthesis (earlier onset, greater extent).
• Dihydrotestosterone (DHT) delayed both spontaneous and DEX-stimulated SPC synthesis.
• Androgens act via the androgen receptor to inhibit DEX-stimulated SPC synthesis.

Conclusions:

• The human fetal adrenal cortex may time lung development through both stimulatory (glucocorticoids) and inhibitory (androgens) mechanisms.
• Androgens can block glucocorticoid-induced surfactant synthesis, suggesting a complex regulatory interplay.
• Fetal adrenal androgens play a significant role in modulating the timing of lung maturation.