NITRIC-OXIDE PRODUCTION BY SERTOLI CELLS IN RESPONSE TO CYTOKINES AND LIPOPOLYSACCHARIDE

Nitric oxide (NO) is formed from L-arginine residues by nitric oxide synthase (NO Synthase) in many types of cells and acts as an intercellular messenger in several physiological systems. In the present study, we demonstrate that a combination (CL) of interleukin-1 alpha, interferon gamma, tumor necrosis factor a and lipopolysaccharide induces nitrite (NO2-) production in cultured rat Sertoli cells. This biosynthesis of NO2- requires a lag time period of 18 hr and then increases for at least 96 hr; it is prevented by two NO Synthase inhibitors, N-G-monomethyl-L-arginine and aminoguanidine. Northern blot analysis shows the induction of a macrophage-like NO Synthase mRNA synthesis in Sertoli cells cultured for a minimum of 6 hr in the presence of CL, with maximal levels after 12 to 30 hr of incubation. These results indicate for the first time that cultured rat Sertoli cells express an inducible NO Synthase isoform in response to a combination of cytokines and lipopolysaccharide. (C) 1995 Academic Press, Inc.