Tissue-specific expression of insulin-like growth factor binding protein-3 protease activity during rat pregnancy

The abundances of insulin-like growth factor binding proteins (IGFBPs) in sera and tissue homogenates of rats at days 12, 15, and 18 of pregnancy were determined by ligand- and immunoblotting. As in serum, IGFBP-3 was abundant in day 12 uterus, placenta, and fetuses, and decreased by day 15. On day 18 of pregnancy, IGFBP-2 was predominant and IGFBP-3 was less than 25% of day 12 values in fetus and placenta, and was undetectable in uterus and decidua. In contrast, IGFBPs in the nonreproductive tissues did not change significantly. IGFBP-3 was more abundant in muscle than heart and liver, and was not detected in lung, kidney, or brain. The decrease in IGFBP-3 in serum and reproductive tissues between days 12 and 15 of pregnancy was temporally related to the appearance of IGFBP-3 protease activity. Proteolytic activity was detectable only at low levels in brain, liver, and spleen, and was undetectable in lung, heart, muscle, and kidney. The specific protease inhibitors that blocked IGFBP-3 proteolytic activities in pregnant rat serum and decidua were virtually identical and suggested inhibition of a divalent cation-dependent tryptic-like serine protease. Furthermore, exposure of bovine IGFBP-3 (in nonpregnant bovine serum) or radiolabeled recombinant human IGFBP-3 to day 18 pregnant rat serum, decidua or uterus resulted in the generation of IGFBP-3 fragments with the same apparent Mrs (29-31 K and 18-23 K). We postulate that tissue-specific degradation may be as important as synthesis in determining IGFBP-3 abundance, and that the dramatic changes in IGFBPs in reproductive and fetal tissues may cause changes in IGF availability which are necessary for rapid tissue growth and differentiation.