Limited proteolysis of the IGF binding protein-2 (IGFBP-2) by a specific serine protease activity in early breast milk

被引:30
作者
Elmlinger, MW
Grund, R
Buck, M
Wollmann, HA
Feist, N
Weber, MM
Speer, CP
Ranke, MB
机构
[1] Univ Tubingen, Childrens Hosp, Pediat Endocrinol Sect, D-72076 Tubingen, Germany
[2] Univ Tubingen, Childrens Hosp, Dept Neonatol, D-72076 Tubingen, Germany
[3] Univ Munich, Klinikum Grosshadern, Dept Med 2, D-81377 Munich, Germany
关键词
D O I
10.1203/00006450-199907000-00013
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
IGF in milk possibly promote maturation of the gastrointestinal tract in newborns. We studied the composition of milk samples derived from 99 healthy women at regular intervals during a period beginning 3 d and ending 6 mo after birth. The concentrations measured by RIA on d 3 were 10.7 +/- 0.4 ng/mL for IGF-II, 1.9 +/- 0.1 ng/mL for IGF-I, 100 +/- 5 ng/mL for IGF binding protein-3 (IGFBP-3), and 2163 +/- 108 ng/mL for IGFBP-2. All factor concentrations decreased by up to 70% in the course of the 6 mo. The most striking Ending was an IGFBP-2-specific protease activity. Protease assays performed by incubation of I-125-IGFBP-2 with milk yielded fragments of 14, 16, 23, and 25 kD. I-125-IGFBP-3 was not cleaved. Proteolysis occurred only in milk from mothers until 4 wk postpartum and could be visualized by immunoblots. Since the affinity of the fragments to I-125-IGF-II was low, they were not demonstrable by ligand blot. Inhibitor studies and pH optimizing classified the IGFBP-2 protease as an Me2+-dependent serine protease with a pH optimum of 7 to 8. The proteolytic activity of further milk proteins, known as IGFBP proteases, was analyzed. Epidermal growth factor receptor peptide and prostate-specific antigen did not cleave IGFBP-2, although the protease activity correlated (r = 0.84, p < 0.00003)With the prostate-specific antigen concentration in milk. The gamma-nerve growth factor cleaved I-125-IGFBP-2, but in a completely different manner than the milk protease. In conclusion, the IGFBP-2 protease in milk is most probably a kallikrein. The specific proteolysis of IGF/IGFBP-2 complexes may increase the biologic availability of IGF in early milk. This mechanism may promote growth of the maternal breast epithelium and maturation of the gastrointestinal tract of newborns.
引用
收藏
页码:76 / 81
页数:6
相关论文
共 24 条
[1]  
Bang Peter, 1995, Progress in Growth Factor Research, V6, P285, DOI 10.1016/0955-2235(96)00007-5
[2]  
Baumrucker C R, 1993, Endocr Regul, V27, P157
[3]   EFFECTS OF DIETARY INSULIN-LIKE GROWTH-FACTOR-I ON GROWTH AND INSULIN-LIKE GROWTH-FACTOR RECEPTORS IN NEONATAL CALF INTESTINE [J].
BAUMRUCKER, CR ;
HADSELL, DL ;
BLUM, JW .
JOURNAL OF ANIMAL SCIENCE, 1994, 72 (02) :428-433
[4]   IMMUNOREACTIVE SOMATOMEDIN-C INSULIN-LIKE GROWTH FACTOR-I AND ITS BINDING-PROTEIN IN HUMAN-MILK [J].
BAXTER, RC ;
ZALTSMAN, Z ;
TURTLE, JR .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1984, 58 (06) :955-959
[5]  
BROWN AL, 1986, J BIOL CHEM, V261, P3144
[6]  
CHARD T, 1994, GROWTH REGULAT, V4, P91
[7]   PROSTATE-SPECIFIC ANTIGEN (PSA) IS AN INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 PROTEASE FOUND IN SEMINAL PLASMA [J].
COHEN, P ;
GRAVES, HCB ;
PEEHL, DM ;
KAMAREI, M ;
GIUDICE, LC ;
ROSENFELD, RG .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1992, 75 (04) :1046-1053
[8]   THE INDUCTION OF A SPECIFIC PROTEASE FOR INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN THE CIRCULATION DURING SEVERE ILLNESS [J].
DAVIES, SC ;
WASS, JAH ;
ROSS, RJM ;
COTTERILL, AM ;
BUCHANAN, CR ;
COULSON, VJ ;
HOLLY, JMP .
JOURNAL OF ENDOCRINOLOGY, 1991, 130 (03) :469-&
[9]   CHANGES IN CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR-I, INSULIN AND GROWTH-HORMONE IN BOVINE MAMMARY-GLAND SECRETION ANTE AND POST-PARTUM [J].
EINSPANIER, R ;
SCHAMS, D .
JOURNAL OF DAIRY RESEARCH, 1991, 58 (02) :171-178
[10]  
Elmlinger MW, 1996, GROWTH REGULAT, V6, P152