Sex hormones influence growth and surfactant production in fetal lung explants

Sex-related differences may be present during fetal lung growth and at the onset of surfactant synthesis. In this study we investigated the role of dihydrotestosterone (DHT) and estrogen (EST) on cell division and on labeled palmitate incorporation into disaturated phosphatidylcholine (DSPC) at various times of gestation. Using organ cultures of fetal rat lung from sexed littermates, it was shown that both DHT and EST reduce DNA synthesis only in tissue taken during the rapid growth phase from day 16 to 19 of gestation. From autoradiographic counts, epithelial cell division was most affected. Both hormones reduced DSPC synthesis in explants prepared at day 18, when levels are normally low. At day 19, DHT reduced palmitate incorporation into DSPC of female explants to the male level; subsequently DHT had no effect on any tissue. In contrast, the addition of EST stimulated DSPC synthesis 40% above controls in both male and female explants taken at day 20 only. The results suggest that sex differences seen in late fetal lung development may arise from the combined effects of slowed epithelial growth induced by these hormones followed by inhibition of DSPC synthesis by DHT and acceleration by EST at the crucial period when surfactant synthesis begins.