Hormonal induction of pulmonary maturation in the rabbit fetus: effects of maternal treatment with estradiol-17 beta on th endogenous levels of cholinephosphate, CDP-choline and phosphatidylcholine.

1. Administration of estradiol-17 beta to pregnant rabbits at 25 days gestation (term, 31 days) resulted n a significant increase in the incorporation of [14C]-choline, but not [14C]ethanolamine, into the lipids of fetal lung slices. The incorporation of [35S]methionine was not affected. 2. Enzymatic assays conducted in vitro revealed no significant effect on either the activities of several enzyme markers for subcellular organelles, the activities of the enzymes responsible for the production of phosphatidylglycerol and phosphatidylinositol, membrane-bound or aqueously dispersed phosphatidate-dependent phosphatidic acid phosphohydrolase activities or the activities of the auxiliary enzymes responsible for the synthesis of dipalmitoylphosphatidylcholine. 3. The activity of the enzymes involved in the choline pathway for the de novo biosynthesis of phosphatidylcholine were not significantly altered except for a 66% increase in the CTP:cholinephosphate cytidylyltransferase activity assayed in the cytosol. The addition of phosphatidylglycerol stimulated cholinephosphate cytidylyltransferase activity approx. 3-fold. However, in the presence of this lipid, the activities in cytosol from control and treated fetuses were similar, indicating that the increased activity noted in the absence of phosphatidylglycerol was due to an activation of existing cytidylyltransferase activity rather than an increase in total enzyme units. 4. Estrogen treatment of the does was also associated with a marked decrease in the levels of cholinephosphate in fetal lung and significant increases in the levels of CDPcholine and phosphatidylcholine. These alterations in pool size are consistent with an increase in the activity of cholinephosphate cytidyltransferase in vivo. The results suggest that cholinephosphate cytidylyltransferase may catalyse an important rate-determining reaction in the synthesis of phosphatidylcholine in fetal lung. The data also support the view that the reaction catalysed by CDPcholine:diacylglycerol cholinephosphotransferase also has a regulatory role during development.