Regulation of decidual IGF-binding proteins and protease activity by placental hormones

Abstract

Summary Regulation of insulin-like growth factor-binding proteins (IGFBPs) produced by cultured decidual cells were evaluated. Ligand blot and immunoblot detected three distinct IGFBPs in medium conditioned by decidual cell culture including IGFBP-1, -2, and -4. Des (1–3) IGF-I suppressed IGFBP-1 and -4 while progesterone stimulated all three IGFBPs when medium was analyzed by ligand blot. Estradiol had no effect on these IGFBPs release by decidual cells. Proteolytic activity in medium conditioned by decidual cells was also evaluated by the proteolysis of nonglycosylated iodinated IGFBP-3. The medium from trophoblast cells obtained from term pregnancy did not degrade intact IGFBP-3. In contrast, the medium from decidual cells and pooled sera from term pregnancy displayed proteolysis of IGFBP-3 with similar proteolytic pattern. Densitometric analysis revealed medium from decidual cell culture degraded IGFBP-3 by 56%. While incubation of decidual cells with estradiol did not alter proteolytic activity in medium, des (1–3) IGF-I slightly stimulated and progesterone completely inhibited proteolysis of IGFBP-3. Since IGF-I and gonadal steroids are produced by placenta, the present study indicates that these placental hormones differentially regulate decidual IGFBPs. Furthermore, these hormones may regulate IGFBPs activities in decidual microenvironment by both synthesis and degradation of these IGFBPs.