Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum and amniotic fluid.

Incubation of iodinated recombinant human insulin-like growth factor binding protein (rhIGFBP)-5 with pregnancy serum or amniotic fluid resulted in the formation of 22- and 15 kDa fragments. Non-pregnancy serum did not contain IGFBP-5 proteolytic activity. Size fractionation revealed the proteolytic activity both in serum and amniotic fluid in a > 100 kDa fraction which co-eluted in gel filtration with proteins of approx. 200 kDa. The IGFBP-5 protease activity was inhibited by EDTA, phenanthroline and PMSF. The formation of proteolytic fragments was also observed using 125I labeled rhIGFBP-3 and -4 but not with rhIGFBP-1 or -6 as substrate. The data demonstrate that pregnancy serum and amniotic fluid contain a very similar cation-dependent serine protease which degrades IGFBP-3, -4 and -5.