BETAMETHASONE ACTIVATION OF CTP-CHOLINEPHOSPHATE CYTIDYLYLTRANSFERASEIS MEDIATED BY FATTY-ACIDS

The purpose of the present study was to determine the mechanisms by wh ich glucocorticoids increase the activity of CTP:cholinephosphate cyti dylyltransferase, a key enzyme required for the synthesis of surfactan t phosphatidylcholine. Lung cytidylyltransferase exists as an inactive , light form low in lipids (L-form) and an active, heavy form high in lipid content (H-form). In vitro, fatty acids stimulate and aggregate the inactive L-form to the active H-form. In vivo, betamethasone incre ases the amount of H-form while decreasing the amount of L-form in fet al lung. There is also a coordinate increase in total free fatty acids in the H-form. In the present study, we used gas chromatography-mass spectrometry to measure the fatty acid species associated with the H-f orms in fetal rat lung after the mothers were treated with betamethaso ne(1 mg/kg). In vivo, betamethasone increased the total amount of free fatty acids associated with the H-form by 62%. Further, the hormone s electively increased the mass of myristic and oleic acids in H-form by 52 and 82%, respectively. However, betamethasone produced the greates t increase in the amount of H-form linoleic acid, which increased four fold relative to control. In vitro, each of the fatty acids increased L-form activity in a dose-dependent manner; however, linoleic acid was the most potent. Linoleic and oleic acids also effectively increased L-form aggregations. These observations suggest that in vivo glucocort icoids elevate the level of specific fatty acids which convert cytidyl yltransferase to the active form. (C) 1995 Wiley-Liss, Inc.