ROLE OF THE TESTIS IN THE RESPONSE OF THE PITUITARY-TESTICULAR AXIS TO NITRIC OXIDE-RELATED AGENTS

Nitric oxide (NO) is generated fi-om the guanidine group of L-arginine by NO synthases (NOS) in a wide variety of tissues, including endocri ne organs. In order to discriminate between central and local effects of NO-related agents on the pituitary-testicular axis, adult rats were injected intraperitoneally with 1 g/kg body weight (bw) L-arginine me thyl ester (GAME, an exogenous substrate of NOS), 0.5 mg/kg bw sodium nitroprusside (SNP, an NO donor) or vehicle (0.9% NaCl) or intratestic ularly with 2 mg/testis L-AME, 2 mu g/testis SNP or 25 mu l vehicle, a nd killed at 60 or 120 min after treatment, Both intraperitoneal and i ntratesticular administration of L-AME had the same effects: a decreas e in the serum concentrations of LH and testosterone and in those of t estosterone in the testicular interstitial fluid. However, treatment w ith SNP was more effective when given intratesticularly, inducing a de crease in serum and interstitial fluid testosterone concentrations, wi thout significant changes in LH concentrations. Furthermore, when rats were injected intraperitoneally with 4 mg L-AME (the same dose as tha t given intratesticularly), serum LH concentrations were not changed, In addition, L-AME administration was not effective in modifying serum LH concentrations in castrated rats, To test the possible role of Ley dig cells, the effects of systemic administration of L-AME were studie d in rats depleted of Leydig cells by treatment with ethylene dimethan e sulphonate, In these animals L-AME significantly decreased serum LH concentrations, To study the role of macrophages in this system, rats depleted of testicular macrophages by the liposome-suicide approach we re injected intraperitoneally (1g/kg bw) or intratesticularly (2 mg/te stis) with L-AME or vehicle, 10 days after macrophage depletion, and k illed at 120 min after treatment, The effects of L-AME on serum LH con centrations were blocked when the drug was administered intratesticula rly.