Glucocorticoid regulation of lung development: lessons learned from conditional GR knockout mice

Area of Science:

• Endocrinology
• Developmental Biology
• Pulmonology

Background:

• Glucocorticoid (GC) steroid hormones regulate systemic homeostasis.
• GCs play a critical, yet less understood, role in fetal lung maturation for birth.
• Synthetic GCs treat preterm infant respiratory distress but have side effects.

Purpose of the Study:

• Review literature on GC roles in fetal lung development.
• Investigate GC actions in specific lung tissue compartments.
• Identify mechanisms for improved therapeutic strategies.

Main Methods:

• Review of recent literature.
• Analysis of global and conditional gene-targeted mouse models.
• Studies of GC deficiency and glucocorticoid receptor ablation.

Main Results:

• GCs thin lung interstitial tissue for efficient gas exchange.
• Mesenchyme is critical for glucocorticoid receptor-mediated lung maturation.
• GCs inhibit cell proliferation and promote epithelial cell differentiation.

Conclusions:

• GCs orchestrate lung development via mesenchymal-epithelial cross-talk.
• Understanding cell-specific GC roles can lead to safer therapeutics.
• Selective GC ligands may reduce side effects for preterm infants.