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INSULIN-LIKE GROWTH FACTOR (IGF) BINDING PROTEIN-3 IN PREGNANCY SERUM BINDS NATIVE IGF-I BUT NOT IODO-IGF-L

Department of Endocrinology, Royal Prince Alfred Hospital Camperdown, NSW 2050, Australia.

Although serum immunoreactive insulin-like growth factor binding protein-3 (IGFBP-3) increases during pregnancy, radioligand binding methods such as ligand blotting with iodinated IGFs fail to detect the protein in pregnancy serum. Since IGFBP-3 must bind IGF-I or IGF-II to form a complex with the acid-labile subunit (-subunit), we have used ternary complex formation from [¹²⁵Ijocsubunit as a measure of IGF binding to serum IGFBP-3. High-pressure liquid chromatography fractions containing IGFBP-3 from pregnancy serum did not bind [¹²⁵I]IGF-I, although the equivalent fractions from nonpregnancy serum showed dose-dependent binding. In contrast, IGFBP-3 fractions from nonpregnancy and pregnancy sera both bound [¹²⁵I]-subunit in the presence of either exogenous IGF-I or endogenous serum IGFs, implying that non-iodinated IGFs could bind to the IGFBP-3. Substitution of nonradioactive iodo-IGF-I for native IGF-I in the complex formation assay confirmed that the pregnancy-induced alteration in IGFBP-3, probably resulting from proteolysis, prevents it from binding iodo-IGF-I while having little effect on its bindiog of the native peptide. This provides an explanation for the failure to detect IGFBP-3 in pregnancy by radioligand binding methods, and raises the question of the significance of proteolysis of IGFBP-3.

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