Evidence to suggest nitric oxide is an interstitial regulator of Leydig cell steroidogenesis

Recent studies have suggested that nitric oxide (NO) may function as both an intracellular and intercellular signal that affects neural and immunological activity, vascular tone, platelet adhesion, and production of some hormones. Arginine analogs such as N^G-monomethyl-l-arginine (l-NMMA) and Nω-nitro-l-arginine methyl ester (l-NAME) act to inhibit the intracellular formation of NO and have been used to study the effects of decreased NO formation on physiological systems. A single in vivo study has suggested that a similar analog, N^G-nitro-l-arginine, increases serum testosterone (T), but the organ site and mechanism of action were not investigated. The present study was performed to investigate the effects of NO synthase inhibitors on Leydig cell function. l-NMMA and l-NAME, but not the inactive enantiomer (d-NMMA), increased both basal and human chorionic gonadotropin (hCG)-stimulated T production while decreasing guanosine 3′:5′-cyclic monophosphate (cGMP). There was no effect on either adenosine 3′:5′-cyclic monophosphate (cAMP) accumulation or specific hCG binding. These results suggest that NO formation, which is inhibited by l-NMMA and l-NAME, is important in the regulation of Leydig cell T production by interstitial cells of the testis, and that changes in cGMP levels might be involved in this process.