Posttranslational modifications of decidual IGFBP-1 by steroid hormones in vitro

Abstract

Insulin-like growth factor binding protein-1 (IGFBP-1) appears to regulate insulin-like growth factors (IGFs; IGF-I and IGF-II) biological activity within the local environment of human placenta by modulating IGFs interaction with their receptors. Considering that posttranslational modifications of IGFBP-1 such as phosphorylation and proteolysis affect its affinity for IGFs, this study was undertaken to identify the role of estrogen and progesterone in this regard. The conditioned media of steroid hormone-treated decidual cells were evaluated using different approaches using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and non-denaturing PAGE following immunoblotting as well as zymographys that contained gelatin and IGFBP-1 as substrates. Our results demonstrated that medroxy progesterone acetate (MPA) treatment increased both phosphorylated and non-phosphorylated decidual-secreted IGFBP-1, whereas 17beta-estradiol (E2) treatment attenuated its phosphorylated forms. Furthermore, the results of zymography revealed that steroid hormones regulated the activity of decidual-secreted matrix metalloproteinases (MMP)-2 and -9, in which E2 treatment up-regulated the MMP-9 activity. Finally, it was demonstrated in our study that decidual-secreted MMP-9 was capable of degrading human amniotic fluid-derived IGFBP-1. In conclusion, our data implicate steroid hormones in the control of IGF system activities at the embryo-maternal interface, at least in part, through their effects on the post-translation changes of decidual-secreted IGFBP-1 such as its phosphorylation and/or proteolysis.