REGULATION OF C6 GLIOMA CELL STEROIDOGENESIS BY ADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE

Incubation of C6 glioma cells in the presence of aminoglutethimide, an inhibitor of cholesterol metabolism, together with either adenosine 3 ',5'-cyclic monophosphate (cAMP) analogues or agents that increase cAM P synthesis, such as cholera toxin, forskolin, and isoproterenol, stim ulated the rate of pregnenolone formation by their isolated mitochondr ia. This effect of cAMP was blocked by the antagonist (Rp)-cAMPS. The incorporation rate of mevalonolactone into pregnenolone was also incre ased by the stimulation of adenylyl cyclase activity in intact C6 cell s. It is concluded that cAMP stimulates glial cell steroidogenesis by increasing the movement of the substrate, cholesterol, to the mitochon dria, where it will be metabolized to pregnenolone by the side chain c leavage cytochrome P450 enzyme. (C) 1994 Wiley-Liss, Inc.