CIRCULATING LEVELS OF IGFS AND IGF BINDING-PROTEINS IN HUMAN CORD SERUM - RELATIONSHIPS TO INTRAUTERINE GROWTH

Cord sera were obtained from 44 term, human infants exhibiting various patterns of intrauterine growth and were assayed for IGF-1, IGF-2, an d IGFBP-1, 2, and 3 by specific RIAs. Serum levels were correlated wit h birth weight (BW), ponderal index (PI), and placental weight (PW). T otal IGF-1 levels correlated significantly with BW (r = 0.392), PW (r = 0.351), and PI (r = 0.481). By contrast, the correlation of IGF-2 wi th birth weight was not statistically significant (r = 0.264, P = 0.09 1). The association of IGF-2 with PI, however, was significant (r = 3. 348, P = 0.024). IGFBP-3 exhibited significant correlations with BW, P I, and PW, similar to those seen with IGF-1. IGFBP-1 and IGFBP-2, howe ver, were not significantly related to growth parameters. IGF-1 levels correlated strongly with IGFBP-3 levels (r = 0.646, P = 0.001). By co ntrast, IGF-1 correlated with the reciprocal of both IGFBP-1 and IGFBP -2. Based upon in vitro affinity constants, theoretical concentrations for each [IGF/IGFBP] complex, free IGFs, and free IGFBPs were calcula ted for each infant. Multiple regression analysis was performed includ ing all 11 calculated variables and correlated with each growth parame ter. This analysis revealed that an integrated expression of IGF activ ity exhibited stronger correlations with growth than each individual p eptide species (BW, r = 0.681; PI, r = 0.660; PW, r = 0.658). These da ta further support roles for IGF related peptides (IGFRPs) in human fe tal and placental growth and suggest regulatory/counterregulatory role s for the IGFBPs. It also supports the hypothesis that individual IGFR Ps interact in a complex manner to define 'net IGF activity' in relati on to fetal growth and/or metabolic status.