EVIDENCE TO SUGGEST NITRIC-OXIDE IS AN INTERSTITIAL REGULATOR OF LEYDIG-CELL STEROIDOGENESIS

Recent studies have suggested that nitric oxide (NO) may function as b oth an intracellular and intercellular signal that affects neural and immunological activity, vascular tone, platelet adhesion, and producti on of some hormones. Arginine analogs such as N-G-monomethyl-L-arginin e (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) act to i nhibit the intracellular formation of NO and have been used to study t he effects of decreased NO formation on physiological systems. A singl e in vivo study has suggested that a similar analog, N-G-nitro-L-argin ine, increases serum testosterone (T), but the organ site and mechanis m of action were not investigated. The present study was performed to investigate the effects of NO synthase inhibitors on Leydig cell funct ion. L-NMMA and L-NAME, but not the inactive enantiomer (D-NMMA), incr eased both basal and human chorionic gonadotropin (hCG)-stimulated T p roduction 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 i n 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. Copyright (C) 1995 by W.B. Saunders Company