Proteolysis of insulin-like growth factor binding protein-3 during rat pregnancy: A role for matrix metalloproteinases

John L. Fowlkes, Ko Suzuki, Hideaki Nagase, Kathryn M. Thrailkill

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Insulin-like growth factor binding protein-3 (IGFBP-3) is degraded by a cation-dependent protease(s) present in the serum of late gestation rats. Proteolysis of IGFBP-3 results in an increase in IGF-I clearance and possibly in IGF bioavailability. Based on our previous findings that matrix metalloproteinases (MMPs) degrade IGFBP-3 in fibroblast conditioned media, we hypothesized that MMPs might be involved in the degradation of IGFBP-3 by rat pregnancy serum. In the present study, we demonstrate that tissue inhibitor of metalloproteinases (TIMP-1), a specific inhibitor of all MMPs, inhibited significantly the degradation of 125I-rhIGFBP-3 by both rat pregnancy serum and rat placental extracts. Purified human MMPs (principally MMP-1 and MMP-3) degraded IGFBP-3 in solution; MMP-3 produced a pattern of IGFBP-3 degradation products identical in size to the fragments produced by pregnancy serum. Furthermore, the combined addition of anti-human MMP-1 IgG and anti-human MMP-3 IgG to rat pregnancy serum blocked almost completely the degradation of 125I-rhIGFBP-3, suggesting that these two MMPs are the principal MMPs involved in IGFBP-3 degradation in rat pregnancy serum. Together, these data suggest that MMPs function as IGFBP-3-degrading proteases in the serum of late gestational pregnant rats.

Original languageEnglish
Pages (from-to)2810-2813
Number of pages4
Issue number6
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Endocrinology


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