Regulation of IGF bioavailability in pregnancy

During pregnancy, insulin-like growth factors (IGFs) are important for grow th of fetal and maternal tissues. One of the IGF binding proteins, IGFBP-1, is thought to regulate their activity within the local environment of the placenta. IGFBP-1 usually exists as a phosphorylated, high affinity species , which sequesters IGFs, thereby inhibiting their actions. This study has i nvestigated the mechanisms that release IGF from IGFBP-1 at the maternal-fe tal interface. Under basal conditions, human decidualized endometrium produ ces both non-phosphorylated (np) and phosphorylated (p) isoforms of IGFBP-1 ; however, in the presence of IGF-II, which is a trophoblast secretory prod uct, npIGPBP-1 was preferentially produced, Furthermore, we found that trop hoblast; presumably via placental alkaline phosphatase, can de-phosphorylat e pIGFBP-1, Since npIGFBP-1 has decreased affinity for IGF-I, these effects should enhance IGF-I bioavailability, In addition, we found that decidual cells produce a protease, which cleaves IGFBP-1, but only when it is non-ph osphorylated; [I-125]-npIGFBP-1 is proteolysed into 14 and 17 kDa fragments which have markedly reduced affinity for IGF, We therefore propose paracri ne modulation of IGFBP-1 at the maternal-fetal interface involving a multi- step process of de-phosphorylation and proteolysis; this will result in enh anced IGF bioavailability and is likely to represent an important mechanism for controlling fetal and maternal tissue growth.