Evidence for the involvement of phospholipase A2 in the regulation of luteinizing hormone-stimulated steroidogenesis in rat testis Leydig cells.

In this study the effects of modulating the release of arachidonic acid by phospholipase A2 (PLA2) on luteinizing hormone (LH)-stimulated testosterone production in rat testis Leydig cells have been investigated. Exogenously added PLA2 significantly stimulated both basal and LH-stimulated testosterone production. The effects of three structurally unrelated PLA2 inhibitors (dexamethasone, quinacrine and p-bromophenacyl bromide (pBPB)) were determined. Dexamethasone and quinacrine caused a dose-dependent inhibition of LH-induced testosterone production but had no effect on LH-induced cyclic AMP accumulation. Dibutyryl cyclic AMP-, and forskolin-stimulated testosterone production were also inhibited by all three inhibitors used. 22R-OH-cholesterol-stimulated testosterone production was not inhibited by quinacrine or dexamethasone showing that they were not exerting their inhibitory effect on LH-induced testosterone production by decreasing the activity of the steroidogenic enzymes. However, pBPB exerted an inhibitory effect on LH-induced testosterone and cyclic AMP production. Furthermore pBPB also inhibited 22R-OH-cholesterol-induced testosterone production illustrating that apart from its well-documented effect on PLA2, it also exerts a direct inhibitory effect on the steroidogenic enzymes. The finding that PLA2 inhibitors inhibit testosterone production without affecting cyclic AMP accumulation provides further indirect evidence for second messengers in addition to cyclic AMP being involved in the action of LH in Leydig cells. These results indicate that PLA2 is involved in LH-induced testosterone production and that cyclic AMP may exert its actions via this pathway.