Epithelial cells are the major site of hydroxysteroid (17β) dehydrogenase 2 and androgen receptor expression in fetal mouse lungs during the period overlapping the surge of surfactant

Many genes involved in the peripheral metabolism of androgens, including hydroxysteroid (17β) dehydrogenases (HSD17B) 2 and 5, steroid 5α reductase 1, and 3α-HSD, are expressed in the developing lung. Because lung development is delayed by androgens and pathologies related to lung immaturity are major concerns for preterm neonates, we are interested in the elucidation of the androgen metabolism in developing lung. In the present report we have identified the cell types expressing HSD17B2 (testosterone into androstenedione) and androgen receptor in normal male and female mouse developing lung between the gestation days 15.5 and 17.5. In situ hybridization and immunohistochemistry revealed that HSD17B2 is expressed in epithelial cells of respiratory and conducting zones, and in mesenchymal cells. The androgen receptor protein was observed in the same cell types that HSD17B2, and in α-smooth muscle actin-positive cells surrounding arteries. No difference was observed for the location of HSD17B2 and androgen receptor expression at any time points studied, or according to sex. Taken together, our results are in concordance with the hypothesis that in mouse fetal lungs the level of androgen receptor occupancy is finely tuned by local HSD17B2 expression.