title: Insulin-like growth factor-binding protein-3 protease activity in Snell normal and Pit-1 deficient dwarf mice.
abstract: Partial proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3) lowers its affinity for IGFs. Presumably, this leads to destabilization of the ternary IGF-IGFBP-3-acid-labile subunit complex in the circulation and an increased bioavailability of IGFs. We investigated the effect of GH on IGFBP-3 proteolysis by comparing serum from normal mice and GH-deficient dwarf mice. While normal mouse serum degraded 125I-IGFBP-3, this activity declined with age. In contrast, serum from dwarf mice displayed strong proteolytic activity at all ages tested (up to 10 weeks). In dwarf mice of 4 weeks and older, this activity could not be inhibited by EDTA and 1,10-phenanthroline, indicating the presence of a divalent cation-independent protease. Prolonged treatment 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 inhibit IGFBP-3 protease activity. GH deficiency therefore appears to induce a new kind of IGFBP-3 protease. Similarly, serum from hypophysectomized rats displayed enhanced IGFBP-3 protease activity compared with control rat serum. These results suggest that a protease induced under conditions of severe GH deficiency may contribute to making IGFs optimally available to the tissues.
authors.affiliation: Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Koedam
authors.forename: C M
authors.initials: CM
authors.lastname: Hoogerbrugge
authors.forename: S C
authors.initials: SC
authors.lastname: van Buul-Offers
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000494:pharmacology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010618:Phenanthrolines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D004492:Edetic Acid; D010450:Endopeptidases; D013006:Growth Hormone; D018972:Insulin-Like Growth Factor Binding Protein 3; D010618:Phenanthrolines; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494187:POU1F1 protein, human; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat; C080473:insulin-like growth factor binding protein-3 protease