Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: quantitative measurements by radioimmunoassay in human fetal serum.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bang
P
P
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Westgren
M
M
Schwander
J
J
Blum
W F
WF
Rosenfeld
R G
RG
Stangenberg
M
M
D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000097:blood*; D017218:Cordocentesis; D005314:Embryonic and Fetal Development; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D011247:Pregnancy; D011863:Radioimmunoassay
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II