Abstract 3

In humans, approximately 75% of IGFs circulate forming a ternary complex (IGFs, IGFBP 3, ALS) with a plasma half-life > 10 hs. The remaining IGFs form binary complexes with other IGFBPs with a mean half life < 30 min. F IGF-1 determined by IMRA would average 1% of total (T). The aim of this study was to determine T, F and non-BP-3b IGF-1 and IGF-2 as a function of age (linear regression) in 132 normal subjects (83 boys [B] and 49 girls [G]), aged 0.16 to 16.6 ys as well as to compare the nmolar concentrations of non-BP3-b and F IGFs with the Kd of type 1 IGF receptor (T1 IGFR). Serum non-BP3-b and F IGF-1 and IGF-2 were determined by calculation using a formula derived from the law of mass action. Serum T IGF-1, T IGF-2 and IGFBP-3 were taken as variables measured by RIA, while IGF-1 and IGF-2 Kd and serum concentrations of IGFBP-1, -2, -5 and -6 were constants taken from published values. Serum IGFBP-3, T IGF-1, T IGF-2 and non-BP3-b IGF-1 increased significatively with age (p<0.0001) while non-BP3-b IGF-2 did not change. The slope of T IGF-1 (B: 15.3, G:16.5) was significantly higher than that of non-BP3-b IGF-1 (B:3.73, G:3.61) p<0.001. Between 0- and 15-y-old, ranges varied as follows: the molar ratio non-BP3-b IGF-2/ non-BP-3-b IGF-1, both sexes: from 10.1 to 2.3; nmolar concentrations of non-BP-3-b IGF-1, B: from 2.12 to 8.95, G: from 2.50 to 9.15; of F IGF-1, B: from 8.3 × 10-5 to 3.9 × 10-4, G from: 9.8 × 10-5 to 4.3 × 10-4. It is concluded that: 1) high levels of IGF-2 might modify the distribution of IGF-1 among IGFBPs; 2) since Kd of T1 IGFR is 1 nM, serum F IGF-1 levels cannot interact with the R; 3) the levels of F IGF-1 measured by IRMA are not compatible with Kds and IGFBPs concentrations. It is proposed that an important fraction of non-BP3-b IGFs represents the bioavailable fraction, as it is suggested by the short half-life of binary complexes.