Betamethasone activation of CTP:cholinephosphate cytidylyltransferase in vivo is lipid dependent.
Glucocorticoids increase surfactant phosphatidylcholine synthesis, in part, by stimulating the rate regulatory enzyme CTP:cholinephosphate cytidylyltransferase. This enzyme exists in mammalian lung cytosol as an active lipoprotein form (H-form) and an inactive apoprotein (L-form) species. We administered betamethasone to pregnant rats to examine the mechanisms for glucocorticoid stimulation of cytidylyltransferase activity in fetal lung. The hormone stimulated cytosolic activity threefold, and this effect was nearly abolished after lipid extraction. The addition of lipid extracts isolated from betamethasone-treated cytosolic preparations to L-form species increased enzyme activity to a greater extent than lipid extracts from control lungs. Further, the glucocorticoid increased the proportion of H-form activity from 34 to 55% of the total activity in the fetal lung cytosol. These changes were associated with a marked decrease in the activity of the L-form species. Analysis of the lipid composition of the H-form revealed that betamethasone increased the content of lipid activators, including phosphatidylglycerol and fatty acids. These observations provide evidence that glucocorticoid stimulation of CTP:cholinephosphate cytidylyltransferase in vivo is mediated by a conversion of the inactive form (L-form) to the active species (H-form). These studies further emphasize the critical role of lung lipids in mediating the glucocorticoid activation of this enzyme.
Mallampalli
R K
RK
Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, Iowa.
Walter
M E
ME
Peterson
M W
MW
Hunninghake
G W
GW
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D019916:Choline-Phosphate Cytidylyltransferase; D004789:Enzyme Activation; D005260:Female; D015151:Immunoblotting; D050356:Lipid Metabolism; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D009713:Nucleotidyltransferases / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats
D001623:Betamethasone; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase