[Regulation of testicular steroidogenesis by nitric oxide]

Testicular macrophages as well as endothelial cells, which are intimately associated with Leydig cells, constitute a potential source of paracrine nitric oxide (NO). In the present study, we investigated the effect of NO donors on MA-10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We observed that NO donors, reversibly inhibit hCG-induced steroidogenesis in both types of cells. We also studied NO mechanism of action. Contrary to what is observed in many other systems, NO inhibitory effect on Leydig cell steroidogenesis is not mediated by cGMP, as 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 gonadotropin action. When we studied NO effect over the steroidogenic pathway in MA-10 cells, we found 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 inhibiting cholesterol side-chain cleavage enzyme (cytochrome P-450 scc) as it does with other heme proteins, including different cytochromes P-450.