Activation of inducible nitric oxide synthase by human choriogonadotropin in RAW 264.7 cells

Although human choriogonadotropin (hCG) plays a crucial role in the regulation of the menstrual cycle and maintenance of pregnancy, little is known about the other functions. However, recently hCG receptors have been identified in nongonadal cells. The objective of the current study was to determine the effect of hCG on the production of nitric oxide (NO). Stimulation of RAW 264.7 cells with hCG after treatment with recombinant interferon-gamma (rIFNgamma) resulted in increased NO synthesis. hCG had no effect on NO synthesis itself. NO production was inhibited by N(G)-monomethyl-L-arginine. rIFNgamma in combination with hCG showed marked increase of the expression of the inducible nitric oxide synthase (iNOS) gene. In addition, synergy between rIFNgamma and hCG was mainly dependent on hCG-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of hCG were endotoxin free. These results suggest that the capacity of hCG to increase NO production from rIFNgamma-primed RAW 264.7 cells is the result of hCG-induced TNF-alpha secretion.