INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN CONCENTRATION AND POSTTRANSLATIONAL MODIFICATION IN EMBRYOLOGICAL FLUID

Levels of proteolytic activity directed against insulin-like growth fa ctor binding protein 3 (IGFBP-3) and the distribution of phosphorylate d isoforms of IGFBP-1 were assessed in matched sample sets of maternal serum, coelomic fluid and amniotic fluid from 21 pregnancies at 6-12 weeks gestation. In addition, concentrations of immunoreactive IGFBP-1 to -3, insulin-like growth factor (IGF)-I and -II were determined in all three compartments in 21 pregnancies, and in coelomic fluid and ma ternal serum in 58 pregnancies. IGF-I concentrations were highest in m aternal serum and similarly low in coelomic and amniotic fluid. IGF-II concentrations were also highest in maternal serum but easily detecta ble in coelomic fluid where concentrations showed a significant correl ation with gestational age. IGFBP-1 concentrations were higher in coel omic fluid than in either maternal serum or amniotic fluid and showed a significant correlation with gestational age in this compartment. An alysis of IGFBP-1 phosphoforms showed clear differences in phosphoryla tion of IGFBP-1 between groups with maternal serum containing predomin antly the phosphorylated forms and coelomic fluid almost exclusively t he non-phosphorylated form. First trimester amniotic fluid IGFBP-1 was barely detectable and appeared non-phosphorylated. These findings sug gest that the high IGF-II concentrations and lack of inhibitory phosph oforms of IGFBP-1 in coelomic fluid could potentially enhance mitogeni c activity in the early human gestational sac. IGFBP-2 concentrations were high in coelomic fluid compared with maternal serum whereas coelo mic fluid IGFBP-3 concentrations were intermediate, easily detectable and correlated strongly with gestational age. Protease activity was fa r less in coelomic fluid than in matched maternal serum samples. Marke d differences in both concentrations and post-translational modificati on of IGFBPs in maternal serum compared with embryonic fluid suggest d ifferent regulatory pathways.