Effect of catecholamines on sterol synthesis in human mononuclear cells

The effect of adrenaline, noradrenaline, isoproterenol and dibutyryl cyclic AMP on the rate of sterol synthesis was studied in freshly isolated human mononuclear cells. Incubation of cells in a medium containing lipid depleted serum led to a two-fold rise in the rate of sterol synthesis from [14C]acetate. Adrenaline, nor-adrenaline and isoproterenol added in a concentration of 2 X 10(-5) mol/l at zero-time resulted in an inhibition of 30% of this increase in sterol synthesis after 4 h, but had no effect when the hormones were given at 4 h. This indicates that the catecholamines require some time to exert their inhibitory action on sterol synthesis. The action of catecholamines on the incorporation of [14C]acetate into sterols could be mimicked by dibutyryl cyclic AMP. Propranolol added in increasing concentrations to the incubation medium diminished or totally prevented the inhibitory effect of adrenaline, noradrenaline and isoproterenol on sterol synthesis. The results indicate that cholesterol synthesis in extrahepatic human cells, regulated predominantly by low density lipoprotein derived from plasma, is under additional control of catecholamines which may act via cyclic AMP.