Insulin-like growth factor (
IGF)-I and -II are known to play a major role in fetal and early postnatal growth. The
IGF binding proteins (IGFBPs) are thought to be important in modulating the actions of the IGFs. In this paper, the effect of
malnutrition in the neonatal rat on serum IGFs and IGFBPs and hepatic
IGFBP messenger (m)
RNA was examined. Control (C) dams (n = 9) were allowed ad libitum intake, whereas restricted (R) dams (n = 9) were limited to 50% of ad libitum intake throughout lactation, which results in decreased milk production and
malnutrition of pups suckling on restricted dams. A subset of pups were cross-fostered from the R-dams to the C-dams from days 15-19 postpartum (PP) to investigate the effect of nutritional repletion (refed). Pups were killed on days 8, 12, 15, and 19 PP and liver and blood collected. Serum
IGF-I and -II concentrations were measured by RIA after
acid-chromatography to remove IGFBPs. Serum IGFBPs were characterized by Western
ligand blot. Hepatic
mRNA for
IGFBP-1, -2, and -3 were determined by northern analysis.
Body weight (BW) of R-pups was significantly less than C-pups by day 10 PP (P less than or equal to 0.05), and mean BW at day 19 was 56% of the C-pups. Refeeding from days 15-19 resulted in a significantly greater rate of growth vs. R-pups (3.2 vs. 0.9 g/day), and mean BW of refed pups at day 19 PP was 75% of C-pups.
Malnutrition caused a significant reduction in both serum
IGF-I and -II after day 12 PP, while causing an elevation in serum
IGFBP-2.
IGFBP-1 and
IGFBP-2 mRNA expression were not significantly affected at days 8 and 12, but were elevated in livers of day 15 and 19 pups.
Malnutrition caused a delay in the development shift from
IGFBP-2 to
IGFBP-3, which normally occurs between day 15 and 19 in the rat. Refeeding raised serum
IGF-I and -II levels to those found in the C-pups and a trend toward normalization of
IGFBP profiles. In conclusion, IGFs and IGFBPs are differentially regulated during neonatal
malnutrition. The decrease in IGF
peptide and induction of
IGFBP-1 and -2 may provide protective mechanisms by inhibiting growth during
malnutrition.