Role of the testis in the response of the pituitary-testicular axis to nitric oxide-related agents.
Nitric oxide (NO) is generated from the guanidine group of L-arginine by NO synthases (NOS) in a wide variety of tissues, including endocrine 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 methyl ester (L-AME, an exogenous substrate of NOS), 0.5 mg/kg bw sodium nitroprusside (SNP, an NO donor) or vehicle (0.9% NaCl) or intratesticularly with 2 mg/testis L-AME, 2 micrograms/testis SNP or 25 microliters vehicle, and killed at 60 or 120 min after treatment. Both intraperitoneal and intratesticular administration of L-AME had the same effects: a decrease in the serum concentrations of LH and testosterone and in those of testosterone in the testicular interstitial fluid. However, treatment with SNP was more effective when given intratesticularly, inducing a decrease in serum and interstitial fluid testosterone concentrations, without significant changes in LH concentrations. Furthermore, when rats were injected intraperitoneally with 4 mg L-AME (the same dose as that 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 Leydig cells, the effects of systemic administration of L-AME were studied in rats depleted of Leydig cells by treatment with ethylene dimethane 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 were injected intraperitoneally (1 g/kg bw) or intratesticularly (2 mg/testis) with L-AME or vehicle, 10 days after macrophage depletion, and killed at 120 min after treatment. The effects of L-AME on serum LH concentrations were blocked when the drug was administered intratesticularly.
Gaytán
F
F
Department of Cell Biology, School of Medicine, University of Córdoba, Spain.
Bellido
C
C
Aguilar
R
R
Morales
C
C
van Rooijen
N
N
Aguilar
E
E
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007985:Leydig Cells / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008264:Macrophages / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D009919:Orchiectomy; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000097:blood
D009599:Nitroprusside; C026512:arginine methyl ester; D009569:Nitric Oxide; D013739:Testosterone; D007986:Luteinizing Hormone; D001120:Arginine