NITRIC-OXIDE INHIBITS LEYDIG-CELL STEROIDOGENESIS

Testicular macrophages as well as endothelial cells, which are intimat ely associated with Leydig cells, constitute a potential source of par acrine nitric oxide (NO) in the testis. In the present study, we inves tigated the effect of NO donors on MA-10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We show that NO donors inhibit h uman CG-induced steroidogenesis in both type of cells. We also studied NO mechanism of action. Contrary to what is observed in many other sy stems, NO inhibitory effect on Leydig cell steroidogenesis is not medi ated by cyclic GMP (cGMP) because NO fails to increase cGMP production , and cGMP analogs do not reproduce NO effect. NO does not modify the production of cAMP, the main second messenger that mediates gonadotrop in action. When we studied NO effect over the steroidogenic pathway in MA-10 cells, we found that NO was inhibiting the conversion of choles terol to pregnenolone. Taken together these results show ad inhibitory effect of NO donors on Leydig cell steroidogenesis, and suggest that NO can be directly inhibiting cholesterol side-chan cleavage enzyme (c ytochrome P450(scc)) as it does with other heme proteins, including di fferent cytochromes P450.