Insulin-Like Growth Factors I and II and Their Binding Proteins in Rat Milk

Abstract

ABSTRACT. IGF-I and -11 are peptide growth factors that may be important contributors to the growth-promoting properties associated with milk. IGF in extracellular fluids, including serum and milk, are carried by specific highaffinity binding proteins (IGFBP). In this study, the levels of IGF-I and -11 in rat serum and milk were quantified by specific RIA, and the IGFBP were characterized using Western ligand blotting and autoradiography throughout lactation. The levels of IGF-I in both milk and maternal serum decreased during lactation. Serum IGF-I decreased from 743 2 187 pglL on d 1 to 391 f 106 (mean f SD) on d 21 of lactation, and milk IGF-I levels fell from 30 +:10 to 13 f 8 pg/L. Levels of IGF-I1 in serum and milk were much lower than IGF-I, and were unaffected by lactation. In maternal serum, several IGFBP were identified: IGFBP-3, which migrates as four glycosylated bands with apparent M, from 38 to 42 kD and one to two nonglycosylated bands with apparent M, of 28 to 29 kD, and an IGFBP with an apparent M, of 24 kD. In milk, IGFBP-3, the 24-kD binding protein, and a third IGFBP with an apparent M, of 29 kD were identified. Treatment of milk and serum with Endoglycosidase F reduced the four glycosylated IGFBP-3 bands (38-42 kD) to two bands with apparent M, of 35 and 32 kD. In rat milk, but not adult rat serum, the IGFBP with an apparent M, of 29 kD was immunoprecipitable by an antibody that recognizes IGFBP-2. These results demonstrate that in adult rat serum and milk both IGF-I and IGF-I1 are present, with IGF-I being predominant. IGFBP are present in rat milk; the presence of IGFBP-2 in rat milk, but not in maternal serum, indicates that IGFBP may be synthesized within the mammary gland. (Pediatr Res 29: 50-55, 1991)

Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Porcine Serum and Milk throughout Lactation

“…In addition, in vitro work has demonstrated that IGFBP modulate the interaction of I G F with its cellular receptors (13). Several IGFBP (IGFBP-3, -2, -1, and -4) have been reported in human, rat, goat, pig, and cow milk (1)(2)(3)(4)(5). The molecular forms of the IGFBP present in milk seem to be species specific; however, IGFBP-2 has been consistently reported in milk.…”

“…Molecular forms of IGFBP were characterized by Western ligand blotting using the method of Hossenlopp er al. (16) as previously described (1,2). Serum samples (4 k L ) were mixed with Laemmli sample buffer (17) and heated at 100°C for 5 min.…”

“…Serum IGF-I was unaffected by duration of lactation. Milk IGF-I1 concentrations were higher than IGF-I concentrations on d [1][2][3][4][5][6][7] postpartum. After d 10, milk IGF-I and IGF-I1 contents were not significantly different.…”

“…Milk IGF binding activity increased between d 1 (28%) and d 3 (44%), then declined until d 28 (7%). Serum IGF-I and IGF-I1 have been found in the milk of all species studied (1)(2)(3)(4)(5). I G F seem to be intricately involved in successful lactation, a s evidenced by their roles in stimulating mammary growth (6), differentiation, and galactopoiesis (7).…”

Intestinal effects of milkborne growth factors in neonates of agricultural importance.

“…Comparing between species, the concentrations of growth factors are significantly higher in the colostrum of agricultural species (porcine, bovine) than in human or rat colostrum; however, species differences in IGF-I levels are no longer apparent in mature milk for review). For example, colostral IGF-I concentrations in the human (Baxter et al, 1984) and rat (Donovan et al, 1991) are two-to threefold higher than those in mature milk, whereas bovine (Vega et al, 1991) and porcine colostrum contain 10-to 500-fold higher levels of IGF-I than mature milk. Although the absolute concentrations of growth factors in colostrum vary between species, the overall profiles throughout lactation are similar among species, showing a marked decline during the transition from prepartum secretions and colostrum to mature milk (Vega et al, 1991;.…”