Am. J. Respir. Cell Mol. Biol., Vol 10, No. 1, 01 1994, 48-57.
Betamethasone activation of CTP:cholinephosphate cytidylyltransferase in vivo is lipid dependent
RK Mallampalli, ME Walter, MW Peterson and GW Hunninghake
Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, Iowa.
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.
