The IGF Axis and Placental Function

Abstract

It is well known that the insulin-like growth factor (IGF) axis is an important regulator of foetal growth and in recent years, it has been suggested that the ligands IGF-I and IGF-II may, in part, mediate this effect by promoting proper placental development and function. In other tissues, IGF effects on metabolism, proliferation and differentiation are primarily mediated via IGF binding protein-regulated interaction of IGFs with the type 1 IGF receptor and therefore here, we review the placental expression and postulated role, of each of the IGF axis components and discuss the cellular mechanisms through which these effects are exerted.

Adhesion Molecules in Human Trophoblast – A Review. I. Villous Trophoblast

“…Signalling through α6β4 can activate the protein tyrosine phosphatase SHP-2, in turn activating the phosphatidylinositol 3-kinase/Akt pathway [12,13], which is important in CTB proliferation in the placental villus [14,15].…”

Maternal serum insulin-like growth factor-binding protein-3 (IGFBP-3) at 11–13 weeks in preeclampsia

“…[16][17][18][19] An endogenous pregnancy-related IGFBP-3 proteolytic activity is considered a fundamental mechanism to increase the bioavailability of IGF-I, [20][21][22] which is a mitogenic polypeptide that stimulates cellular proliferation and differentiation and is involved in the regulation of trophoblast invasion and placental development. [23][24][25] In addition, IGFBP-3 can inhibit cell proliferation and stimulate apoptosis via non-IGFdependent pathways. 16,26 Thus, IGFBP-3 has important roles in regulating many aspects of placental development and fetal growth.…”

Recent Insights into the Role of the Insulin-Like Growth Factor Axis in Preeclampsia

“…Since the discovery of the IGF system before 50 or so years, there is ample evidence for their role in cell proliferation, differentiation and migration and their anti-apoptotic properties as well; thus they are involved in several physiological and pathological processes during prenatal and postnatal life [Forbes & Westwood, 2008]. This review aims to critically evaluate the postulated role of IGF axis components in the pathogenesis of preeclampsia and to discuss the mechanisms through which these effects are mediated.…”

“…Although in the non-pregnant state, IGFBP-I is mainly produced in the liver, during pregnancy its predominant site of synthesis is the decidualized endometrium [Forbes & Westwood, 2008].…”

“…The exact impact of IGFBPs also depends on the posttranslational modification of the protein (e.g. phosphorylation, glycosylation, altered proteolysis) which is under rapid and dynamic regulation [Forbes & Westwood, 2008]. Specifically, the IGFBP-I gene has multiple regulatory elements in its promoter that synergize or act independently and it is strongly regulated by insulin though IGFBP-3 is primarily determined by GH [Powell et al, 1995].…”