IN-VITRO REGULATION OF AN INDUCIBLE-TYPE NO SYNTHASE IN THE RAT SEMINIFEROUS TUBULE CELLS

Rat Sertoli cells express an inducible nitric oxide synthase isoform ( iNOS) in response to the combined addition of the cytokines-interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleuk in-1 alpha (IL-1 alpha)-and lipopolysaccharides (LPS). We demonstrated that the addition of cytokines and lipopolysaccharides (C+L) to cultu red peritubular cells resulted in high nitrite and iNOS mRNA levels, i ndicating the induction of an iNOS isoform. This enzyme was not induce d in cultured pachytene spermatocytes or spermatids. Nitrite productio n in Sertoli cells and peritubular cells required both IFN gamma and T NF alpha and was potentiated by LPS, whereas IL-la was ineffective. Th e induction of nitrite production and iNOS mRNA by IFN gamma+TNF alpha +LPS could be further enhanced by basic fibroblast growth factor in Se rtoli cells but not in peritubular cells. In contrast, transforming gr owth factor beta markedly reduced this induction in peritubular cells but had no effect on Sertoli cells, FSH positively modulated the C+L-i nduced INOS in Sertoli cells. Dibutyryl cAMP had a synergistic effect with C+L on NOS activity in both Sertoli cells and peritubular cells. In contrast, testosterone did not influence basal or induced NOS activ ity in these two cell types. These data show that NOS activity in the somatic cells of the seminiferous tubules is induced and regulated by multiple factors that act in combination, and suggest that nitric oxid e may participate in the endocrine and paracrine control of testicular function.