The Phosphorylation Pattern of Insulin-Like Growth Factor-Binding Protein-1 in Normal Plasma Is Different from That in Amniotic-Fluid and Changes During Pregnancy

Westwood, M; Gibson, J M; Davies, A J; Young, R J; White, A

Journal of Clinical Endocrinology & Metabolism. 1994;79(6):1735-1741.

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We have determined the phosphorylation pattern of circulating insulin-like growth factor-binding protein-1 (IGFBP-1) in normal subjects and assessed how this changes in pregnancy. Two RIAs employing different monoclonal antibodies (MAbs 6303 or 6305) were used to measure IGFBP-1. In normal subjects, RIA 6303 measured ii-fold higher levels than RIA 6305 (72.8 vs. 6.6 mu g/L; P < 0.008). However, in amniotic fluid (AF), the two assays gave similar results. Immunoprecipitation of plasma and AF with MAb 6303 and 6305 before nonsodium dodecyl sulfate-electrophoresis and Western ligand blotting revealed different IGFBP-1 isoforms and differential antibody recognition as the cause of this discrepancy. In AF, both MAbs precipitated nonphosphorylated and phosphorylated isoforms, whereas in plasma, only a single highly phosphorylated species, not seen in AF, was observed. This form of IGFBP-1 was precipitated by MAb 6303 only. During pregnancy, the phosphorylation state of IGFBP-1 in the maternal circulation was altered, as nonphosphorylated IGFBP-1 and three lesser phosphoforms were also observed. The appearance of these other variants resulted in a significant increase in IGFBP-1 measured by RIA 6305 (37, 51, and 83 mu g/L in first, second, and third trimesters, respectively; P < 0.0005 vs. controls). The changes in IGFBP-1 phosphorylation induced by pregnancy may influence the modulatory effects of IGFBP-1 on IGF bioavailability and, hence, fetal growth.

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Created by:
Gibson, Martin
15th January, 2012, 15:04:11
Last modified by:
Gibson, Martin
Last modified:
1st February, 2013, 19:47:01

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