DEVELOPMENTAL REGULATION OF THE SOLUBLE FORM OF INSULIN-LIKE GROWTH-FACTOR-II MANNOSE 6-PHOSPHATE RECEPTOR IN HUMAN SERUM AND AMNIOTIC-FLUID

The insulin-like growth factor II/mannose 6-phosphate receptor (IGF-II /MPR) has a specific binding site for IGF-II, a fetal mitogen. In rode nts, IGF-II/MPR expression declines dramatically after birth. To see w hether such developmental regulation occurs in humans, we studied the ontogeny of the soluble form of IGF-II/MPR in amniotic fluid (AP) and serum. Phosphomannan-affinity purified AF IGF-II/MPR was a single band of approximately 220 kDa, like the band in serum, and it bound IGF-II with affinity identical to that of the membrane-associated form. By q uantitative immunoblot, the soluble IGF-II/MPR in serum and AF was fou nd to undergo developmental regulation that parallels that of the rode nt, although it is much less pronounced quantitatively. The highest le vels are seen in midgestation, decreasing at term in both serum and AF . In serum, they further decline to one-third of the preterm levels by adulthood. As part of characterizing AF IGF-II binding, we also show that the prominent high-molecular mass IGF-II-binding protein in prete rm AF is GPC3, a protein of the glypican family, recently cloned becau se its mutations predispose to Wilms' tumor. For the first time, we sh ow that IGF-II binding to this protein is saturable, and therefore spe cific. These findings should promote understanding of the role of IGF- II and its binding proteins in human development.