Alteration in IGF-I binding in the cerebral cortex and cerebellum of neonatal rats during protein-calorie malnutrition.
Neonatal brain development in the rat is adversely affected by malnutrition. Alterations in tissue binding of IGF-I in the malnourished brain were tested in rat pups from mothers who were fed a 20% protein diet (C) or a 4% protein diet (M) starting from day 21 of gestation and continued throughout suckling. IGF-I binding in both cortex and cerebellum decreased progressively in C and M groups from day 6 to day 13. At day 9, 11, and 13, the binding was significantly greater (p < 0.02) in M compared to C groups. To investigate whether these changes might be related to the alteration in receptor activity, membranes were incubated with 125I-IGF in the presence of excess insulin with or without unlabeled IGF-I. In the absence of insulin, specific IGF-I binding in the M group was increased by 41.8 +/- 13.8% (mean +/- SEM p < 0.05) relative to C group. Insulin produced a consistent but incomplete inhibition of binding in both C and M, of 75% and 67% respectively. In addition, the specific IGF-I binding in the presence of insulin was increased in M group by 70.2 +/- 9.4% relative to C, p < 0.05. To characterize the nature of this binding, cerebral cortical membranes, from both groups, incubated with 125I-IGF-I were cross-linked, and electrophoresed on 6% and 10% SDS-PAGE gels under reducing conditions. Autoradiography of the 6% gel showed two specific bands at 115 kD and 240 kD, consistent with monomeric and dimeric forms of the IGF-I receptor, which were inhibited by excess insulin. In contrast, a 10% gel showed an additional band at 35 kD (IGF-binding protein) that was not inhibited by insulin. In both gels, membrane preparations from the M group showed a heightened intensity of the bands relative to C. The increase in binding protein relative to the receptor suggests a disequilibrium that may limit the availability of exogenous IGF-I to the tissues.
Maheshwari
H G
HG
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Mermelstein
S
S
vonSchlegell
A S
AS
Shambaugh
G E
GE
D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000037:antagonists & inhibitors; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D011485:Protein Binding; D011502:Protein-Energy Malnutrition / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors
D018969:Insulin-Like Growth Factor Binding Proteins; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I