Insulin-Like Growth Factors and Binding Proteins in Early Milk from Mothers of Preterm and Term Infants

Abstract

Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother’s milk and digestion of ¹²⁵I-IGF-II and ¹²⁵I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 ± 0.2 vs. 2.3 ± 0.1 ng/ml), IGF-II (12.0 ± 0.4 vs. 12.2 ± 0.5 ng/ml), IGFBP-3 (100.0 ± 5.1 vs. 80.0 ± 5.8 ng/ml), but did so for IGFBP-2 (3,144 ± 172 vs. 2,428 ± 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of ¹²⁵I-IGFBP-2 and partial cleavage of ¹²⁵I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants.

Temporal Changes in Insulin-Like Growth Factors I and II and in Insulin-Like Growth Factor Binding Proteins 1, 2, and 3 in Human Milk

“…It is likely that IGFBP-2 plays a particular role to facilitate delivery of IGF-II to the gut. Recent data demonstrated that complexed IGF-II/IGFBP-2 is protected from gastric cleavage, whereas individually both were highly degraded [10]. Thus these data strongly indicate that substantial amounts of both are likely to reach the gut intact and functional [10].…”

“…This may indicate active secretion of IGFBP-2 into milk or enhanced production within the mammary gland. In contrast, IGFBP-3 and IGF-I form a ternary complex in plasma with the acid-labile subunit that is unlikely to pass the endothelial barrier [10]. Thus, the IGFBP-3 present in human milk may represent local mammary expression of IGFBP-3, possibly induced by growth hormone.…”

“…Early studies suggested that the milk IGF-I levels may show a late rise between the 1st and the 6th week after parturition, while the levels of other proteins decrease [8]; more recent data suggest a progressive decline over the first 6 months of life [9]. Similarly, milk IGFBP-3 levels, but not IGFBP-2 or IGF-I or IGF-II levels, were recently reported to decline between 7 and 21 days in mothers of both term and preterm infants [10]. The aim of the present study was to evaluate the postpartum time course of changes in IGFs and their binding proteins.…”

Effects of Different CMV-Heat-Inactivation-Methods on Growth Factors in Human Breast Milk

“…The RIAs were competitive binding assays for serum utilizing 125 I-labeled IGF-1, IGF-2, IGFBP-2, or IGFBP-3. Using human milk whey as the assay matrix instead of serum, the RIAs had been evaluated previously for linearity, precision, and recovery (7,8, and unpublished data). The precision of measurement of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were 7.5, 8.9, 7.8, and 9.2% coefficient of variation (CV), respectively.…”

“…To avoid the IGF measurement interfering with the IGFBPs present in breast milk, we used IGF-1 and IGF-2 assays that made use of the principle of excess IGF-2 or IGF-1, respectively. This is a standard approach to make IGFBP assays more reliable (7,8). The sensitivity of all assays was Ͻ0.2 ng/mL.…”