INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 PROTEASE ACTIVITY IN SNELL NORMAL AND PIT-1 DEFICIENT DWARF MICE

Partial proteolysis of insulin-like growth factor-binding protein-3 (I GFBP-3) lowers its affinity for IGFs. Presumably, this leads to destab ilization of the ternary IGF-IGFBP-3-acid-labile subunit complex in th e circulation and an increased bioavailability of IGFs. We investigate d the effect of GH on IGFBP-3 proteolysis by comparing serum from norm al mice and GH-deficient dwarf mice. While normal mouse serum degraded I-125-IGFBP-3, this activity declined with age. In contrast, serum fr om dwarf mice displayed strong proteolytic activity at all ages tested (up to 10 weeks). In dwarf mice of 4 weeks and older, this activity c ould not be inhibited by EDTA and 1,10-phenanthroline, indicating the presence of a divalent cation-independent protease. Prolonged treatmen t with GH (4 weeks) did not decrease the overall potency of the serum to degrade IGFBP-3, but partially restored the ability of EDTA to inhi bit IGFBP-3 protease activity. GH deficiency therefore appears to indu ce a new kind of IGFBP-3 protease. Similarly, serum from hypophysectom ized rats displayed enhanced IGFBP-3 protease activity compared with c ontrol rat serum. These results suggest that a protease induced under conditions of severe GH deficiency may contribute to making IGFs optim ally available to the tissues.