REGULATION OF TESTICULAR STEROIDOGENESIS BY NITRIC-OXIDE

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 present study, we investigated the ef fect of NO donors on MA-10 murine Leydig tumor cell line and rat Leydi g cell steroidogenesis, We observed that NO donors, reversibly inhibit hCG-induced steroidogenesis in both types of cells. We also studied N O mechanism of action. Contrary to what is observed in many other syst ems, NO inhibitory effect on Leydig cell steroidogenesis is not mediat ed by cGMP, as NO fails to increase cGMP production and cGMP analogs d o not reproduce NO effect. NO does not modify the production of cAMP, the main second messenger that mediates gonadotropin action. When we s tudied NO effect over the steroidogenic pathway in MA-10 cells, we fou nd that NO is inhibiting the conversion of cholesterol to pregnenolone . Taken together these results show an inhibitory effect of NO donors on Leydig cell steroidogenesis and suggest that NO can be directly inh ibiting cholesterol side-chain cleavage enzyme (cytochrome P-450scc) a s it does with other heme proteins, including different cytochromes P- 450.