Dynamic lipid changes in rapidly proliferating hepatic smooth endoplasmic reticulum during acute dexamethasone...

The regulation by the cell of subcellular membrane components is dependent on a highly complex balance of nutritional, hormonal and metabolic events. We have characterized the lipid components of the endoplasmic reticulum (ER) of the liver of adrenalectomized (ADX) rats and the response of these membrane components to glucocorticoid administration. Membrane microviscosity as measured by fluorescence depolarization of 1,6-diphenylhexatriene (DPH) was measured and correlated with lipid composition and content of the membranes. In the ADX rat, a significant increase in membrane microviscosity of the smooth endoplasmic reticulum (SER) was observed and this was accompanied by an increase in the cholesterol content/mg protein and a decrease in the phospholipid content/mg protein. A change in the fatty acyl chain composition is observed with a significant increase in the mole percentage of arachidonic acid (20:4) and an accompanying decrease in saturated fatty acids. Within 2-6 hr of dexamethasone administration, a decrease in membrane microviscosity is observed that returns this value to one similar to that for normal control animals. Both the cholesterol and the phospholipid contents/mg protein are likewise restored to levels similar to that for control animals beginning at the 2-hr time point. The arachidonic acid and saturated fatty acid content of the constituent phospholipids do not begin to return to values similar to those for control animals until 6 hr after dexamethasone administration. From these experiments, we can conclude that glucocorticoids play a significant regulatory role in determining the lipid properties of rat hepatic microsomal membranes.