Testosterone inhibits expression of inducible nitric oxide synthase in murine macrophages

We investigated the effect of testosterone, the main sexual steroid hormone in men, upon inducible nitric oxide synthesis in murine macrophages. Incub ation of murine macrophages (RAW 264.7 cells) stimulated by bacterial. lipo polysaccharide (2 mug/ml) with increasing amounts of testosterone (0.1-40 m uM) showed a dose dependent inhibition of inducible nitric oxide synthesis. Inducible nitric oxide synthase protein expression was reduced in a dose d ependent manner as revealed by immunoblotting when cells were incubated wit h increasing amounts of testosterone. This was associated with a decline in iNOS mRNA-levels as determined by competitive semiquantitative PCR. As nit ric oxide plays an important role in immune defense and atherosclerosis pre vention, testosterone-induced iNOS inhibition could lead to an elevated ris k of infection as well as to the development of atherosclerotic lesions. (C ) 2000 Elsevier Science Inc. All rights reserved.