title: The hypothalamo-pituitary axis responses to lipopolysaccharide-induced endotoxemia in mice lacking inducible nitric oxide synthase.
abstract: Nitric oxide (NO) generated by inducible NO synthase (iNOS) may be implicated in the biological responses of the central nervous system to immune stimuli. To elucidate the role of iNOS in the hypothalamo-pituitary axis in responses to endotoxemia, using iNOS knockout (KO) mice, we examined the levels of c-fos, a neural activational marker, and corticotropin-releasing hormone (CRH) gene transcription in the paraventricular nucleus (PVN) and central amygdala (CeAMY) during lipopolysaccharide (LPS)-induced endotoxemia. In addition, the serum adrenocorticotropic hormone (ACTH) levels were also examined during endotoxemia. Following the intraperitoneal administration of LPS (1 mg/kg), the levels of the c-fos gene expression significantly increased in the PVN and the CeAMY regardless of the genotype. However, the disruption of the iNOS gene resulted in a significant decrease in the c-fos gene induction in the PVN in comparison to that observed in control mice. LPS administration caused a significant increase in CRH mRNA levels in the PVN and CeAMY regardless of genotype. However, the LPS-induced upregulation of CRH mRNA was significantly attenuated in the PVN of iNOS KO mice in comparison to that in the control mice. In contrast, no such genotype differences in the neural activity or CRH gene transcription were observed in the CeAMY. The serum ACTH responses to LPS were also significantly blunted in the iNOS KO mice in comparison to the control mice. These results suggest that iNOS-derived NO may therefore play a stimulatory role in the activity of the hypothalamo-pituitary axis during endotoxemia.
authors.affiliation: Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Akasaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Hisae
authors.initials: H
authors.lastname: Nishii
authors.forename: Naohiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D052247:Nitric Oxide Synthase Type II