Summary17P-Estradiol (0.44 to 4.4 &kg) was intramuscularly administered to pregnant rabbits on day 25 or 26 of gestation, and the fetuses were delivered by cesarean section 24 hr later. On light microscopy, the lungs from the treated group had larger alveoli and thinner interalveolar septa than did those from the controls at the same gestational age. The 1umen:septa ratio was 0.62 + 0.06 in the control group and 0.88 + 0.05 in the treated group ( P < 0.01). Blood vessels in the lungs of the treated group were also more mature than were those in the control group. Alveolar epithelial cells consisted of 52% undifferentiated, 21% type 11, and 27% type I cells in the control group. In the estrogen-treated group, the corresponding distribution was 25, 29, and 45%. There were 0.82 -+ 0.16 lamellar bodies per alveolar cell in the treated group compared to 0.38 k 0.06 in the controls (P < 0.05). Estrogen decreased fetal lung glycogen content from 247 + 15 pg/mg protein to 70 9 on day 26 and from 103 -+ 13 to 13 + 2 on day 27 ( P < 0.001). Estrogen administration increased the rate of incdrporation of choliie into phosphatidylcholine in fetal lung slices. decreased the rate of thymidine incorporation into DNA, but had no effect on the rates bf incorporatibn of ethanolamine into phosphatidylethanolamine or of leucine into protein. These data indicate that estrogen accelerates the rate of fetal lung maturation. It appears to stimulate lung differentiation at the expense of lung growth. SpeculationEstrogen may be involved in the physiologic control of fetal lung maturation and pulmonary surfactant production.We have previously shown that administration of 17/3-estradiol to pregnant rabbits at 25 to 26 days gestation (term is 31 days) accelerates fetal lung maturation and stimulates production of pulmonary surfactant (16,17). Thus, maternal estrogen administration has the following effects on the fetal lung: it increases the amount of total phospholipid and phosphatidylcholine as well as the phosphatidylcholine:sphingomyelin ratio in lung lavage (17), it increases the rate of choline incorporation into phosphatidylcholine in lung slices (16), and it increases the activities of pulmonary cholinephosphate cytidylyltransferase and lysolecithin acyltransferase (16), enzymes involved in the synthesis of total and disaturated phosphatidylcholine, respectively (33). Gross et al. (12) reported that estrogen accelerates maturation of fetal rat lung in organ culture. This fmding suggests that estrogen has a direct effect on the fetal lung.The purpose of the present study was to further characterize the effects of estrogen on fetal lung maturation. Inasmuch as there are distinct morphological changes during maturation of the fetal lung (2), we examined the effects of estrogen on these parameters of lung maturation. In addition, we determined the effect of estrogen on lung glycogen content because this decreases toward the end of gestation in a number of species (4,23,36), and it has been postulated that glycogen may provide substrate o...