Essential Intracrine Androgenic Action in Lung Development for Both Sexes.

Area of Science:

• Developmental biology
• Endocrinology
• Pulmonology

Background:

• Hormonal regulation of lung development is complex.
• Androgens may play a positive role in lung maturation despite known negative effects.
• Hyperoxia models alveolar simplification seen in bronchopulmonary dysplasia.

Purpose of the Study:

• To assess the impact of blocking androgen and estrogen actions on lung development.
• To investigate the effects of excess androgens and estrogens during critical lung development stages.
• To examine these effects under normal oxygen and hyperoxia conditions.

Main Methods:

• Mouse lung development was studied at postnatal day 9.
• Exposure to normal (21%) or high (80%) oxygen was administered from days 1-4.
• Hormonal manipulation involved administering vehicle, flutamide (antiandrogen), dihydrotestosterone (androgen), fulvestrant (antiestrogen), or 17β-estradiol (estrogen) from days 3-8.

Main Results:

• Flutamide significantly altered lung morphometrics under normal oxygen.
• Under hyperoxia, both flutamide and dihydrotestosterone similarly affected lung parameters.
• Specific changes included reduced small air spaces (<1000 μm²) and increased large air spaces (>2500 μm²) after flutamide treatment.

Conclusions:

• Endogenous androgens play a vital intracrine role in lung development during the saccular to alveolar transition.
• Excess androgens are detrimental to lung development when combined with hyperoxia.
• Endogenous estrogens showed no significant impact on lung development in this window; exogenous estrogens had minor effects.