Regulation of the splenic somatotropic axis by dietary protein and insulin-like growth factor-I in the rat.
Protein intake is a critical regulatory factor of the GH/IGF-I axis. Recently, it has been shown that splenic GH/IGF-I may respond to nutritional stress by preserving tissue homeostasis. To study the effects of exogenous administration of rhIGF-I on the splenic GH/IGF-I axis in protein malnourished rats, six-week-old male rats were assigned to one of four isocaloric diets differing in the protein content (0%, 4%, 12% and 20%) for a period of 12 days. Animals in the same dietary group on day 5 were randomly divided into two groups and during 7 days received a continuous subcutaneous infusion of either vehicle or rhIGF-I (300 microg/day). A low protein intake decreased the circulating levels of IGF-I, IGFBP-3, GH and insulin whereas the serum levels of IGFBP-1 were increased. Splenic IGFBP-3, -4 and -6 mRNA expression were up-regulated by protein malnutrition. Similarly, IGF-IR and GHR mRNA expression were significantly increased by the lack of dietary protein, whereas the levels of IGF-I mRNA remained unchanged. Exogenous rhIGF-I administration increased the circulating levels of IGFBP-1 and -3 in protein malnourished rats and reduced significantly the GH and insulin levels in well-fed rats. Similarly, rhIGF-I increased significantly the expression of the GHR in the spleen and splenic weight in all dietary groups, whereas nitrogen balance was enhanced only in the high-protein diet group. Among the cell subpopulations, B lymphocytes showed the highest GHR expression. These results suggest that in catabolic stress, induced by protein malnutrition the splenic GH/IGF-I axis is an important modulator and contributes to the maintenance of the homeostasis of the immune system.
Mejia-Naranjo
Wilson
W
Department of Chemistry, National University of Colombia, P.O. Box 14490, Bogota, Colombia.
Yakar
Shoshana
S
Bernal
Rosalina
R
LeRoith
Derek
D
Sanchez-Gomez
Myriam
M
D000818:Animals; D004044:Dietary Proteins / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013002:Somatomedins / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
D004044:Dietary Proteins; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone