EFFECTS OF NITRIC OXIDE-RELATED AGENTS ON OPIOID REGULATION OF RAT TESTICULAR STEROIDOGENESIS

These studies examined whether nitric oxide (NO) mediates opioid suppr ession of testicular steroidogenesis, Adult male rats were treated wit h various combinations of a NO synthase (NOS) inhibitor (N-G-nitro-L-a rginine methyl ester; NAME), a NO donor (isosorbide dinitrate; ISDN), an opioid agonist (morphine), and an opioid antagonist (naltrexone), S erum LH and testosterone and testicular interstitial fluid (TIF) testo sterone concentrations were then measured, Inhibition of NO production by NAME reversed morphine-suppressed testosterone secretion; treatmen t with the NO donor, ISDN, reversed naltrexone-stimulated testosterone secretion, NAME did not alter morphine's effects on LH secretion and attenuated morphine's suppression of hCG-stimulated testosterone secre tion, indicating that these effects occur directly in the testes and a re not dependent on LH secretion, Even though these effects suggested possible interactions between NO and opioid systems, no additive or sy nergistic effects were found with suppressive combinations of morphine and ISDN, or with stimulatory combinations of naltrexone and NAME at doses that had little effect on testosterone secretion when given alon e. These results indicate that opioid and NO exert independent effects on testicular steroidogenesis through separate pathways or mechanisms and that NO does not mediate opioid-induced testicular suppression.