Abstract 323
Poster Session IV, Tuesday, 5/4 (poster 298)
Delayed lung maturation and lower levels of surfactant phospholipid have been previously identified in male fetuses compared to females in several species. Phosphatidylcholine, the principle surfactant phospholipid is produced in the lung via the CDP-choline pathway. We investigated the mechanisms for sex- differences in surfactant content by examining parameters of phosphatidylcholine turnover and biosynthesis; the latter was evaluated by measuring metabolic steps within the CDP-choline pathway. Compared to male lung cells, freshly isolated lung cells from female fetuses contained higher levels of disaturated phosphatidylcholine (DSPC), a marker of surfactant lipid. Female mixed monolayer cultures exhibited a 71% increase in choline incorporation into DSPC compared to male cultures. Male cultures exhibited significantly greater release of [ 3H]-arachidonic acid into the medium compared to females, suggesting sex-differences in phospholipase activity. However, pulse-chase studies demonstrated no differences in degradation of DSPC between the sexes. Direct assays of phospholipase A2 (PLA2), phosphatidylcholine -specific phospholipase C (PC-PLC), and phospholipase D (PLD) also showed no significant differences between the groups. Female mixed lung cells, however, had greater rates of cellular choline transport and activity of cytidylyltransferase, the rate-regulatory enzyme for phosphatidylcholine synthesis. There were no sex differences in the activities of choline kinase, cholinephosphotransferase, or intracellular pool sizes of choline or cholinephosphate. These studies indicate that sex differences in surfactant phospholipid content are not due to differences in phospholipid turnover, but rather differential regulation of specific metabolic steps within the surfactant biosynthetic pathway.
