Major secretory product of the mesometrial decidua in the rat, a variant of alpha-2-macroglobulin, binds insulin-like growth factor I via a protease-dependent mechanism

• Type: Article in International Scientific Journal
• Date: 1996

Authors

daSilva, GC (Author) Other; Teixeira, N (Author) FFUP; Bell, SC (Author) Other

Journal

Title: Molecular Reproduction and Development

Vol. 44

Pages: 103-110

ISSN: 1040-452X

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 12 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-001-ED2

DOI: 10.1002/(sici)1098-2795(199605)44:1<103::aid-mrd12>3.0.co;2-5

Abstract (EN): Decidualization-associated protein (DAP), the quantitatively major secretory product of the mesometrial decidua in the rat, is a pl variant of the liver-derived acute-phase reactant, alpha-2-macroglobulin (alpha(2)M), alpha(2)M, a broad spectrum protease inhibitor, has been demonstrated in the human to bind a variety of cytokines and growth factors. In humans, the quantitatively major secretory product of decidual tissue is an insulin-like growth factor (IGF) binding protein. In this study, we have therefore tested the ability of liver- and decidual-derived alpha(2)M in the rat to bind IGF-I. alpha(2)M purified from acute-phase plasma and DAP purified from cytosolic extracts of decidual tissue and medium from tissue incubations both bound radiolabeled IGF-I. The binding of IGF-I was principally dependent upon the coincubation of the protein with a proteinase. Therefore, it occurred during the conversion of the ''slow'' to the ''fast'' form of alpha(2)M. Pretreatment with proteinase to produce the fast form before addition of the IGF-I reduced the binding. Binding was enhanced at a ratio protein:proteinase of 1:1. Results from gel electrophoretic analysis were consistent with the covalent linkage of IGF-I to alpha(2)M during the cleavage of the ''bait region.'' A saturable displacement by increasing concentrations of unlabeled IGF-I suggested high affinity interaction. Under conditions of demonstrated binding to purified proteins binding in acute-phase plasma, decidual tissue extracts and tissue incubation medium were associated with a high molecular weight species which was confirmed to represent alpha(2)M and DAP, respectively. Our studies demonstrate that IGF-I may now be added to the list of regulatory peptides which alpha(2)M may bind and that, in rat decidua, DAP may represent the functional homolog of decidual IGFBP-1 in the human and regulate growth factor function during placental development. (C) 1996 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8