Endotoxin administration increases hypothalamic somatostatin mRNA through nitric oxide release.
Acute inflammation induced by endotoxin (LPS) administration inhibits insulin-like growth factor (IGF-I) and growth hormone (GH) secretion. The aim of this study was to elucidate the role of glucocorticoids and nitric oxide (NO) in the effect of LPS on hypothalamic somatostatin gene expression. Adult male Wistar rats were injected with different doses of LPS (5, 10 and 100 microg/kg). Rats received two i.p. injections of LPS (at 17:30 and 8:30 h the following day) and were killed 4 h after the second injection. LPS administration at the dose of 100 microg/kg increased the hypothalamic somatostatin mRNA content, as well as the serum concentrations of corticosterone. Glucocorticoids do not seem to be involved in LPS-induced increase in hypothalamic somatostatin mRNA since adrenalectomy did not prevent this effect. In order to analyze the possible effect of NO, aminoguanidine, an inducible nitric oxide synthase inhibitor, was injected (100 mg/kg s.c.) simultaneously with LPS injection. Aminoguanidine administration did not modify somatostatin mRNA in saline injected rats, but it prevented LPS-induced increase in hypothalamic somatostatin mRNA. These data suggest that the stimulatory effect of endotoxin on hypothalamic somatostatin gene expression is not mediated by glucocorticoids, but instead by the increase in NO release.
Priego
Teresa
T
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain.
Ibáñez de Cáceres
Inmaculada
I
Martín
Ana Isabel
AI
Villanúa
M Angeles
MA
López-Calderón
Asunción
A
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000235:genetics*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D013004:Somatostatin; D003345:Corticosterone