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-l7 beta (E2) and progesterone (P4) 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 P4 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.
Miller
L
L
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, USA.
Alley
E W
EW
Murphy
W J
WJ
Russell
S W
SW
Hunt
J S
JS
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D005938:Glucocorticoids; D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D009569:Nitric Oxide; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase