title: Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production.
abstract: The present study was designed to investigate the effect of lipopolysaccharide (LPS) on the expression levels and activities of the nitric oxide synthase (NOS) and heme oxygenase (HO) systems in the rat adrenal gland. Both enzymatic activities were significantly increased in this tissue after in vivo treatment with LPS. The concurrent induction of the HO-1, NOS-1, and NOS-2 gene products was also detected as both mRNAs and protein levels were augmented by this treatment in a time-dependent way. A significant interaction between both signaling systems was also demonstrated as in vivo blockage of NOS activity with N(G)-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in HO expression and activity levels, while an increase in NOS activity was observed when HO was inhibited by Sn-protoporphyrin IX (Sn-PPIX). As both NOS and HO activities have been previously involved in the modulation of adrenal steroidogenesis, we investigated the participation of these signaling systems in the adrenal response to LPS. Our results showed that acute stimulation of steroid production by ACTH was significantly increased when either NOS or HO activities were inhibited. We conclude that adrenal NOS and HO can be induced by a non-lethal dose of endotoxin supporting a modulatory role for these activities in the adrenal response to immune challenges.
authors.affiliation: Departmento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 5, Buenos Aires C1121ABG, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Grion
authors.forename: E M
authors.initials: EM
authors.lastname: Repetto
authors.forename: Y
authors.initials: Y
authors.lastname: Pomeraniec
authors.forename: C Martinez
authors.initials: CM
authors.lastname: Calejman
authors.forename: F
authors.initials: F
authors.lastname: Astort
authors.forename: R
authors.initials: R
authors.lastname: Sanchez
authors.forename: O P
authors.initials: OP
authors.lastname: Pignataro
authors.forename: P
authors.initials: P
authors.lastname: Arias
authors.forename: C B
authors.initials: CB
authors.lastname: Cymeryng
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000032:analysis / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; C032628:tin protoporphyrin IX; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D051547:Heme Oxygenase-1; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone