TY - JOUR
T1 - Regulation of the splenic somatotropic axis by dietary protein and insulin-like growth factor-I in the rat
AU - Mejia-Naranjo, Wilson
AU - Yakar, Shoshana
AU - Bernal, Rosalina
AU - LeRoith, Derek
AU - Sanchez-Gomez, Myriam
N1 - Funding Information:
We thank Jennifer Setser for her technical assistance, Dr. Leonardo Lareo and Dr. Maria Fernanda Gutierrez at Universidad Javeriana, Colombia for their help with the animal facility; Claudia Murcia and Hernando Vanegas for their help with the statistics. The study was supported by Colciencias, Colombia and the International Program in the Chemical Sciences, IPICS (to W.M.-N., R.B. and M.S.-G.) Uppsala University, Sweden.
PY - 2003/10
Y1 - 2003/10
N2 - 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 μg/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.
AB - 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 μg/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.
KW - GH/IGF-I axis
KW - GHR
KW - IGF-I
KW - IGF-IR
KW - IGFBP
KW - Lymphocytes
KW - Nitrogen balance
KW - Protein malnutrion
KW - Rat
KW - Spleen
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U2 - 10.1016/S1096-6374(03)00014-5
DO - 10.1016/S1096-6374(03)00014-5
M3 - Article
C2 - 12932746
AN - SCOPUS:0141854330
SN - 1096-6374
VL - 13
SP - 254
EP - 263
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 5
ER -