272 A ROLE FOR PROLACTIN, CORTISOL AND INSULIN IN PHOSPHATIDYLGLYCEROL SYNTHESIS BY HUMAN FETAL LUNG

Abstract

Late in human gestation, the fetal lung synthesizes increased amounts of phosphatidylcholine (PC) followed in time, by an increase in phosphatidylglycerol (PG) synthesis with concomitant decrease in phosphatidylinositol (PI) synthesis. We reported previously that prolactin (P), cortisol (F) and insulin (I), in combination, stimulate PC synthesis and surfactant secretion by mid-trimester human fetal lung explants cultured in serum-free medium. Therefore, we examined the effect of these hormones on the relative amounts of PG and PI in surfactant. Lung tissue explants from 20-24 wk human abortuses were maintained for 7 d in medium without hormones (control) or with P (2.5 μg/ml), F (0.2 μg/ml) and I (2.5 μg/ml) added alone or in various combinations. During the last 24 h of culture [14C]glycerol (1 μC/ml) was added to the medium. A lamellar body (LB) fraction was isolated and the percent incorporation of [14 C] into LB glycerolipids was measured using two-dimensional TLC. The incorporation of [14C] into PC was 74% in all groups. In control explants [14C] incorporation into PG was 3.9% and into PI was 7.1% (PG/PI = 0.7). P+F+I and F+I increased significantly [14C] incorporation into PG (11.9% and 10.9%, respectively) and decreased [14C] incorporation into PI (3.5% and 4.1%, respectively). These treatments increased the PG/PI ratio (F+P+I = 3.5; F+I = 2.7). F and F+P also increased PG/PI (2.2 and 2.0, respectively). These results are suggestive that PG and PI synthesis in human fetal lung are under multi-hormonal control.