Inducible nitric oxide synthase in the rat testis: evidence for potential roles in both normal function and inflammation-mediated infertility.
In vitro data have indicated that nitric oxide (NO) inhibits Leydig cell testosterone production, suggesting that NO may play a role in the suppression of steroidogenesis and spermatogenic function during inflammation. Consequently, we investigated expression of the inflammation-inducible isoform of NO synthase (iNOS) in the inflamed adult rat testis and the ability of a broad-spectrum inhibitor of NO production, L-nitro-L-arginine methyl ester, to prevent Leydig cell dysfunction during inflammation. Unexpectedly, immunohistochemical and mRNA data established that iNOS is expressed constitutively in Leydig cells and in a stage-specific manner in Sertoli, peritubular, and spermatogenic cells in the normal testis. Expression was increased in a dose-dependent manner in all these cell types during lipopolysaccharide (LPS)-induced inflammation. In noninflamed testes, treatment with the NO synthase inhibitor reduced testicular interstitial fluid formation and testosterone production without any effect on serum LH levels. Administration of the inhibitor did not prevent the suppression of testicular interstitial fluid and testosterone production that occurs within 6 h after LPS treatment. Collectively, these data indicate a novel role for iNOS in autocrine or paracrine regulation of the testicular vasculature, Leydig cell steroidogenesis, and spermatogenesis in the normal testis. The data suggest that increased NO is not the major cause of acute Leydig cell dysfunction in the LPS-treated inflammation model, although a role for NO in this process cannot be excluded, particularly at other time points. Moreover, up-regulation of iNOS may contribute to the seminiferous epithelium damage caused by LPS-induced inflammation.
O'Bryan
M K
MK
Monash Institute of Reproduction and Development, Monash University, Clayton, 3168, Australia.
Schlatt
S
S
Gerdprasert
O
O
Phillips
D J
DJ
de Kretser
D M
DM
Hedger
M P
MP
D000818:Animals; D015152:Blotting, Northern; D016208:Databases, Factual; D006728:Hormones / Q000097:blood; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007248:Infertility, Male / Q000201:enzymology*; D007249:Inflammation / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000201:enzymology* / Q000502:physiology
D006728:Hormones; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat