Effects of nitric oxide-related agents on rat testicular function

M. L. Adams, E. R. Meyer, B. N. Sewing, T. J. Cicero

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113 Scopus citations


The effects of nitric oxide (NO)-related agents on testicular function were examined in male rats with measurements of serum luteinizing hormone, serum testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes. Serum and TIF testosterone levels and luteinizing hormone secretion were significantly decreased by the NO donor, isosorbide dinitrate (ISDN), and the NO synthase (NOS) substrate, L-arginine methyl ester, a source for the endogenous production of NO. The effects of ISDN on TIF volumes were inconsistent, but L-arginine methyl ester decreased TIF formation in a dose- dependent manner. In addition, ISDN dose dependently suppressed testosterone secretion stimulated by human chorionic gonadotropin treatment, suggesting that the effects on testosterone secretion were independent of changes in secretion of the endogenous gonadotropin luteinizing hormone. ISDN, L- arginine methyl ester, and the endogenous NOS substrate L-arginine completely blocked testosterone secretion stimulated by the NOS inhibitor N(G)-nitro-L- arginine methyl ester (NAME), whereas the relatively inactive NOS substrate, D-arginine, only partially blocked NAME-stimulated testosterone secretion. Hydralazine and nicardipine, two vasodilators that do not exhibit prominent NO-related effects, also blocked basal testosterone secretion and testosterone secretion stimulated by the vasoconstrictor NAME. These results suggest that 1) NO suppresses a major regulatory aspect of testicular function, testosterone secretion, 2) the stimulatory effects of the NOS inhibitor NAME on testosterone secretion are caused by NOS inhibition and a decrease in NO production, 3) the vasoactive effects of NO and NOS inhibitors, rather than direct steroidogenic effects, may mediate these effects on testicular function, and 4) arginine-NOS-NO pathways may play an important role in male reproductive endocrine function and fertility.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - 1994


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