Reduction in Cell-Associated Low Density Lipoprotein in Dexamethasone-Treated HeLa Cells: Suggested Mechanism*

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Abstract
An earlier study of cholesterol metabolism in human cervical carcinoma HeLa cells has provided evidence for the inhibitory effect of glucocorticoids on de novo cholesterol synthesis. To extend this observation to other regulatory pathways involving cholesterol, the effects of dexamethasone were determined on the cell-associated low density lipoprotein (LDL) assumed to represent a normal source of exogenous cholesterol. HeLa cells internalized LDL by low affinity and high affinity saturable processes. Since cell-associated LDL was reduced by dexamethasone to 20-60% of the control value, further attempts were made to examine the nature of this observation. The kientics of LDL-cell association and the binding stuides performed at 4.degree. C indicated that dexamethasone did not affect the immediate binding of LDL to HeLa cells, whereas 25-hydroxycholesterol, which is known in other cells to inhibit LDL binding by reducing the number of LDL receptors, had the same effect in HeLa cells. The nature of the dexamethasone effect appeared to be related to interference with processing of bound LDL after its internalization. Further evidence that dexamethasone did not affect the initial binding of LDL was provided by the experiments in which chloroquine completely abolished the inhibitory action of dexamethasone.