Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: Quantitative measurements by radioimmunoassay in human fetal serum

Peter Bang, Magnus Westgren, Júrg Schwander, Werner F. Blum, Ronald (Ron) Rosenfeld, Magnus Stangenberg

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Abstract

There is evidence for a role for IGF-I in the endocrine control of human fetal growth despite the low serum IGF-I concentrations. The formation in serum of binary complexes between IGF-I or -II and either of six IGF binding proteins (IGFBP-1 to -6) and, in particular, of long-lived ternary complexes between IGF-I or -II, IGFBP-3, and acid-labile subunit is thought to regulate IGF-I bioavailability by increasing its serum half-life. The present study assesses the bioavailability of circulating IGF-I in 19- to 35-wk gestation human fetuses in utero 1) by quantitative RIA measurements of IGF and IGFBP in serum and 2) by examining whether serum proteolysis of IGFBP-3 may further increase IGF-I bioavailability. Fetal serum concentrations of IGFBP-3, IGF-I, and IGF-II were low with marked or only modest increases with gestational age (p <0.001, p <0.005, and p <0.05, respectively). The mean molar ratio between IGF-I plus -II and IGFBP-3 demonstrated a molar excess of IGF (50%) similar to that in adolescents but in contrast to the 1:1 molar ratio in adults. The median IGFBP-2 concentration was 3-fold elevated to a molar concentration similar to that of IGFBP-3 (adult serum displays 10-fold higher IGFBP-3 concentrations). The median serum IGFBP-1 concentration was not elevated as previously reported in newborns. IGFBP-3 protease activity was not increased in fetal serum, in contrast to pregnancy serum and amniotic fluid. Nevertheless, IGFBP-3 protease activity did interfere with IGFBP-3 determinations by Western ligand blotting, and IGFBP-1 and IGFBP-2 levels obtained by this technique did not correlate with concentrations determined by RIA, stressing the importance of quantitative IGFBP measurements. In summary, increased IGF-I bioavailability in the human fetus is suggested by the molar excess of IGF over IGFBP-3 and the increase in IGFBP-2, which do not form a long-lived ternary complex. The lack of suppression of fetal serum IGFBP-1 may suggest that the delivery of IGF-I to the tissues is normal.

Original languageEnglish (US)
Pages (from-to)528-536
Number of pages9
JournalPediatric Research
Volume36
Issue number4
StatePublished - 1994
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor I
Radioimmunoassay
Insulin-Like Growth Factor Binding Protein 3
Serum
Biological Availability
Insulin-Like Growth Factor Binding Proteins
Fetus
Pregnancy
Insulin-Like Growth Factor II
Amniotic Fluid
Fetal Development
Proteolysis
Gestational Age
Half-Life
Western Blotting

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Bang, P., Westgren, M., Schwander, J., Blum, W. F., Rosenfeld, R. R., & Stangenberg, M. (1994). Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: Quantitative measurements by radioimmunoassay in human fetal serum. Pediatric Research, 36(4), 528-536.

Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3 : Quantitative measurements by radioimmunoassay in human fetal serum. / Bang, Peter; Westgren, Magnus; Schwander, Júrg; Blum, Werner F.; Rosenfeld, Ronald (Ron); Stangenberg, Magnus.

In: Pediatric Research, Vol. 36, No. 4, 1994, p. 528-536.

Research output: Contribution to journalArticle

Bang, P, Westgren, M, Schwander, J, Blum, WF, Rosenfeld, RR & Stangenberg, M 1994, 'Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: Quantitative measurements by radioimmunoassay in human fetal serum', Pediatric Research, vol. 36, no. 4, pp. 528-536.
Bang, Peter ; Westgren, Magnus ; Schwander, Júrg ; Blum, Werner F. ; Rosenfeld, Ronald (Ron) ; Stangenberg, Magnus. / Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3 : Quantitative measurements by radioimmunoassay in human fetal serum. In: Pediatric Research. 1994 ; Vol. 36, No. 4. pp. 528-536.
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abstract = "There is evidence for a role for IGF-I in the endocrine control of human fetal growth despite the low serum IGF-I concentrations. The formation in serum of binary complexes between IGF-I or -II and either of six IGF binding proteins (IGFBP-1 to -6) and, in particular, of long-lived ternary complexes between IGF-I or -II, IGFBP-3, and acid-labile subunit is thought to regulate IGF-I bioavailability by increasing its serum half-life. The present study assesses the bioavailability of circulating IGF-I in 19- to 35-wk gestation human fetuses in utero 1) by quantitative RIA measurements of IGF and IGFBP in serum and 2) by examining whether serum proteolysis of IGFBP-3 may further increase IGF-I bioavailability. Fetal serum concentrations of IGFBP-3, IGF-I, and IGF-II were low with marked or only modest increases with gestational age (p <0.001, p <0.005, and p <0.05, respectively). The mean molar ratio between IGF-I plus -II and IGFBP-3 demonstrated a molar excess of IGF (50{\%}) similar to that in adolescents but in contrast to the 1:1 molar ratio in adults. The median IGFBP-2 concentration was 3-fold elevated to a molar concentration similar to that of IGFBP-3 (adult serum displays 10-fold higher IGFBP-3 concentrations). The median serum IGFBP-1 concentration was not elevated as previously reported in newborns. IGFBP-3 protease activity was not increased in fetal serum, in contrast to pregnancy serum and amniotic fluid. Nevertheless, IGFBP-3 protease activity did interfere with IGFBP-3 determinations by Western ligand blotting, and IGFBP-1 and IGFBP-2 levels obtained by this technique did not correlate with concentrations determined by RIA, stressing the importance of quantitative IGFBP measurements. In summary, increased IGF-I bioavailability in the human fetus is suggested by the molar excess of IGF over IGFBP-3 and the increase in IGFBP-2, which do not form a long-lived ternary complex. The lack of suppression of fetal serum IGFBP-1 may suggest that the delivery of IGF-I to the tissues is normal.",
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AU - Stangenberg, Magnus

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