The role of arachidonic acid on LH-stimulated steroidogenesis and steroidogenic acute regulatory protein accumulation in MA-10 mouse Leydig tumor cells

Metabolic pathways leading to the production of arachidonic acid (AA) and i ts metabolites have been reported to have modulatory effects on steroidogen esis in a number of cell types. To examine the importance of the arachidoni c acid pathway in steroid production and steroidogenic acute regulatory (St AR) protein expression, luteinizing hormones (LH) or N-6-2-o-dibutyryl-aden osine-3:5-cyclic monophosphate(Bt(2)cAMP) stimulated MA-10 mouse Leydig tum or cells were treated with various concentrations of quinacrine (an inhibit or of arachidonic acid production). Incubation of the cells with quinacrine resulted in dose-dependent decreases in steroid production and StAR protei n. Twenty micromolars quinacrine inhibited 92 and 91 % of LH-induced proges terone and StAR protein, respectively, and 98 and 90% of Bt(2)cAMP-induced progesterone and StAR protein. Reversal of this inhibition was obtained by incubation of quinacrine-treated cells with various levels of AA, which res ulted in a dose-dependent increase in both steroid and StAR protein levels. Two hundred micromolars of AA rescued 57 and 60% of the LH-induced steroid production and StAR protein, respectively, and 52 and 89% of Bt(2)cAMP-ind uced steroid production and StAR protein. These results suggest that the ef fect of AA on LH- and cAMP-stimulated steroidogenesis is associated with th e modulation of StAR protein expression.