Effects of endotoxin lipopolysaccharide administration on the somatotropic axis.
The aim of this work was to study the effect of chronic activation of the immune system on the somatotropic axis. Accordingly, the changes in growth hormone (GH) secretion, circulating insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in response to endotoxin lipopolysaccharide (LPS) administration were examined in adult male Wistar rats. Acute LPS injection (2.5, 25 or 250 microg/kg) increased serum corticosterone in a dose-dependent manner and decreased serum levels of insulin and IGF-I, serum GH concentration declined linearly as the LPS dose increased. Western ligand blot showed an increase in the 33 kDa band (corresponding to IGFBP-1 and IGFBP-2) in the rats that received the highest dose of LPS (250 microg/kg). Chronic LPS administration (250 microg/kg daily for 8 days) significantly decreased body weight, serum levels of IGF-I and pituitary GH content, whereas it increased circulating IGFBP-3 (47 kDa band), IGFBP-1 and IGFBP-2 (33 kDa band) and the 24 kDa band (which possibly corresponds to IGFBP-4). Serum concentration of corticosterone and hypothalamic somatostatin content were also increased by chronic LPS treatment. These data suggest that the decrease in GH and IGF-I secretion and the increase in circulating IGFBPs are important mechanisms in body weight loss during chronic inflammation.
Soto
L
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Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Martín
A I
AI
Millán
S
S
Vara
E
E
López-Calderón
A
A
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000032:analysis / Q000097:blood*; D007031:Hypothalamus / Q000737:chemistry; D007249:Inflammation; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000032:analysis; D013997:Time Factors
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D008070:Lipopolysaccharides; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003345:Corticosterone