The sex difference in type II cell surfactant synthesis originates in the fibroblast in vitro.

Lung from 19 days' gestation male and female rat fetuses was grown in mixed monolayer culture. Cultures from female lungs synthesized twice as much 3H-saturated phosphatidylcholine (3H-SPC) from 3H-choline as cultures from male lungs. Preincubation with cortisol caused a doubling in 3H-SPC synthesis by cultures from both sexes. Study of sex-specific fibroblast cultures revealed significantly higher 11-oxidoreductase activity and basal and cortisone- or cortisol-stimulated fibroblast-pneumonocyte factor activity in female cultures. In contrast to the findings in the fibroblast cultures, sex-specific type II cell cultures showed no difference in basal 3H-SPC synthesis or in response to cortisol-stimulated fibroblast-conditioned medium. Furthermore, the type II alveolar cells had no 11-oxidoreductase activity. These data indicate that there are sex differences in both cortisol metabolism and fibroblast-pneumonocyte factor production by the fetal lung fibroblast. These differences would lead to a sex difference in the synthesis of pulmonary surfactant.