Progesterone inhibits inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages

The purpose of this study was to determine whether the female hormones estradiol-17 beta (E2) and progesterone (PF) influence inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-activated mouse macrophages. Treatment with P4 alone caused a time- and dose-dependent inhibition of NO production by macrophage cell lines (RAW 264.7, J774) and mouse bone marrow culture-derived macrophages as assessed by nitrite accumulation, RAW 264.7 cells transiently transfected with an iNOS gene promoter/luciferase reporter-gene construct that were stimulated with IFN-gamma/LPS in the presence of PP displayed reduced luciferase activity and NO production, Analysis of RAW 264.7 cells by Northern blot hybridization revealed concurrent P4-mediated reduction in iNOS mRNA. These observations suggest that P4-mediated inhibition of NO may be an important gender-based difference within females and males that relates to macrophage-mediated host defense.