Regulation of insulin-like growth factor-binding protein-3 ternary complex formation in pregnancy.
The IGFs are believed to be important in pregnancy and are implicated in the pathophysiology of pre-eclampsia. In adults the IGFs circulate primarily with IGF-binding protein-3 (IGFBP-3) and an acid-labile glycoprotein (ALS) in a 140 kDa complex which limits IGF bioavailability. Less than 10% of IGFBP-3 is in lower molecular weight forms. We have investigated the developmental regulation of the IGF/IGFBP system in normal and pre-eclamptic pregnancies with particular emphasis on the IGFBP-3 ternary complex. Circulating levels of IGF-I, IGFBP-3 and ALS, and their degree of association in the ternary complex in the fetus increased with gestational age. In neonatal serum from deliveries <35 weeks' gestation IGFBP-3 was predominantly in 30-50 kDa form(s) and ALS was a limiting factor for ternary complex formation. In serum from deliveries >35 weeks both ALS and IGFs were limiting but approximately 25% of IGFBP-3 was unable to form the ternary complex even in the presence of excess ALS and IGF-I. Serum IGFBP-1, -2 and -6 concentrations tended to decrease with increasing gestational age. In pre-eclamptic pregnancies, amniotic fluid IGFBP-2, -3 and -6 levels decreased with gestational age while IGFBP-1 levels did not show the normal decline. We speculate that the endocrine IGF system develops in the fetus during the third trimester of pregnancy when ALS levels increase.
Lewitt
M S
MS
Department of Endocrinology, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
Scott
F P
FP
Clarke
N M
NM
Wu
T
T
Sinosich
M J
MJ
Baxter
R C
RC
D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D000704:Analysis of Variance; D002850:Chromatography, Gel; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005865:Gestational Age; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008970:Molecular Weight; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy
D015292:Glycoprotein Hormones, alpha Subunit; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018976:Insulin-Like Growth Factor Binding Protein 6; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II