title: Growth hormone increases inducible nitric oxide synthase expression in mesangial cells.
abstract: Mice transgenic for bovine growth hormone (GH) develop progressive glomerulosclerosis. However, the proximal signaling events that lead to increased matrix deposition in this pathologic condition are still unclear. Components of the L-arginine metabolic pathway, especially inducible nitric oxide (NO) synthase (iNOS), ornithine aminotransferase (OAT), and ornithine decarboxylase (ODC), have been associated with glomerular scarring. In this study, mesangial cells were treated with GH, and the expression of iNOS, ODC, and OAT was determined using reverse transcription-PCR. In addition, nitrite accumulation in the conditioned media of mesangial cell cultures was measured in the presence or absence of GH. The findings revealed that GH increased iNOS transcript levels in a dose-dependent manner, with the highest levels being attained at GH concentrations of 20 to 50 ng/ml. The GH-induced increase in iNOS transcript levels was accompanied by a significant increase in nitrite concentrations in conditioned media, which was blocked by the addition of L-N(G)-monomethylarginine. The effect of GH (50 ng/ml) in eliciting nitrite production was as potent as that of bacterial lipopolysaccharide (10 microg/ml). The expression of OAT and ODC, in contrast, was not altered at any of the GH concentrations tested. GH receptor mRNA was also expressed by mesangial cells, independently of the GH concentration present in the cell culture medium. These data indicate that GH may interact with its receptor to regulate the L-arginine/NO pathway in mesangial cells, by directly modulating iNOS expression and NO production, without altering the arginase/OAT/ODC pathway.
authors.affiliation: Department of Medicine, Division of Nephrology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Sonia Q
authors.initials: SQ
authors.lastname: Doi
authors.affiliation: Renal Cell Biology Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Jacot
authors.affiliation: Department of Medicine, Division of Nephrology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Sellitti
authors.affiliation: Department of Medicine, Division of Nephrology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Hirszel
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.affiliation: Department of Medicine, University of Miami School of Medicine, Miami, Florida.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Striker
authors.affiliation: Department of Medicine, University of Miami School of Medicine, Miami, Florida.
authors.forename: Liliane J
authors.initials: LJ
authors.lastname: Striker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013006:Growth Hormone / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009953:Ornithine-Oxo-Acid Transaminase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D019323:omega-N-Methylarginine; D013006:Growth Hormone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D009953:Ornithine-Oxo-Acid Transaminase; D009955:Ornithine Decarboxylase