Endocrine Abstracts

The insulin-like growth factors (IGFs) are important regulators of cellular function, with effects on growth, survival and metabolism mediated primarily through the type 1 IGF receptor (IGFIR). Recent work suggested that localisation of IGFIR to a subset of lipid rafts, known as caveolae, may be important for IGF function. In this study we have investigated whether these membrane domains were involved in IGF-I-mediated cell survival by comparing signalling in caveolae-positive...

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In humans, the exchange of nutrients and waste between mother and fetus occurs via the outer layer of the placenta (syncytium; ST); this layer is maintained by continuous growth and differentiation of underlying cytotrophoblasts (CT). Pregnancy complications such as intrauterine growth restriction are associated with abnormal CT proliferation and apoptosis; altered levels of maternal insulin-like growth factors (IGFs) have also been reported in these conditions. We have demons...

The insulin-like growth factors (IGFs) signal through the type 1 IGF receptor (IGFIR) to regulate cellular proliferation and survival. A current theory suggests that a subset of plasmalemmal lipid rafts, termed caveolae, may orchestrate such IGF-mediated signalling.In order to investigate the role of caveolae and the marker protein caveolin in controlling IGF signals, two cell models of caveolin deficiency were generated. Using shRNA, caveolin-1 expressi...

Conditions such as pre-eclampsia and intrauterine growth restriction highlight the importance of normal placental cell turnover for successful pregnancy outcome. In these conditions abnormal levels of proliferation and increased apoptosis have been reported; aberrations in components of the IGF axis have also been observed. IGFs regulate proliferation and survival in other cellular systems but their ability to influence human placental cell function remains to be established.<...

Growth in utero depends on adequate development and function of the fetal / maternal interface. During pregnancy, the insulin-like growth factors (IGFs), which are known to be critically involved in placental development, are controlled by a binding protein - IGFBP-1 - produced by maternal decidualised endometrium. We have recently found that decidua also produces a protease which cleaves IGFBP-1 into fragments that are unable to bind ligand. This study aimed to identif...

Background: Infants born small for gestational age (SGA) usually show catch-up growth during the first few years of post-natal life. However, some infants remain small and little is known about the factors governing their growth failure. IGF-I receptor mutations account for a minority of cases therefore we have initiated an assessment of signalling molecules downstream of the receptor.Method: Skin biopsies were obtained with local ethics approval from he...

Objective: Insulin-like growth factor-II (IGF-II), a critical regulator of placental development, enhances proliferation and survival of human cytotrophoblasts by signalling through the IGF-1 receptor (IGF-1R). Excess IGF-II binds to IGF-2R, which mediates its transport to the lysosomes for degradation. Although considered to act solely as an IGF-II clearance receptor, IGF-2R has been implicated in mediating IGF-II-stimulated migration and invasion in trophoblast. We therefore...

Insulin-like growth factor (IGF-I) is an important signal for mammary gland development and epithelial cell survival. Following lactation, the mammary gland undergoes involution through extensive epithelial cell apoptosis and thus, the IGF-I survival signal must be inhibited. IGF actions are regulated by association with high affinity binding proteins (IGFBPs) and the aim of this study was to investigate the expression of IGFBPs during mouse mammary gland development to determ...

Background: Approximately 1000 children per annum born small for gestational age (SGA) will fail to catch-up and become eligible for GH treatment. The reason for this failed growth is often not defined. Understanding mechanisms that cause growth failure in SGA and finding potential biomarkers of poor growth is therefore important. We are using the new technique of Metabolomics as one avenue to address this. Metabolomics is the quantification of small molecule metabolites in a ...