Searchable abstracts of presentations at key conferences in endocrinology

ea0034oc2.6 | Endocrine regulation of cell behaviour | SFEBES2014

A potential role for food-derived microRNAs in human placental development

Timms Kate , Westwood Melissa , Forbes Karen

Normal placental and fetal growth are important for neonatal and lifelong health. Placental growth is influenced by endogenous microRNAs (miRs) which regulate translation of their target genes into proteins. Recently, plant miRs from ingested food have been detected in mammalian circulation; maternal fruit and vegetable intake is important for normal development but the underlying mechanisms are not well understood. We hypothesised that miRNAs from maternal dietary fruit and v...

ea0021oc4.5 | Bone and parathyroid | SFEBES2009

Dicer-dependant microRNAs regulate IGF-actions in the human placenta

Forbes Karen , Aplin John , Westwood Melissa

Fetal growth restriction is associated with abnormal placental cell (cytotrophoblast) proliferation. Using an explant model of human first trimester placenta, we have demonstrated that the IGFI and -II stimulate proliferation in cytotrophoblast and are probably essential for normal placental growth. IGF activates signalling through both Akt and ERK, so the regulation of these pathways in placenta is important for normal pregnancy outcome. The tissue contains high levels of mic...

ea0015oc14 | Reproduction | SFEBES2008

IGF-mediated cell turnover in the human placenta is positively regulated by the protein tyrosine phosphatase, SHP-2

Forbes Karen , Aplin John D , Westwood Melissa

Pregnancy complications such as pre-eclampsia and intrauterine growth restriction are associated with abnormal placental cell (cytotrophoblast; CT) proliferation and apoptosis. The mechanisms regulating these events are unclear however altered levels of IGFs have also been reported in these conditions. Using an explant model of human first trimester placenta we have shown that both IGF-I and –II act through IGF1R mediated signalling pathways to enhance CT proliferation, d...

ea0013p262 | Reproduction | SFEBES2007

IGFBP-3 has both IGF-dependent and –independent effects on cytotrophoblast proliferation in the human placenta

Forbes Karen , Aplin John D , Westwood Melissa

IGF-I and -II influence cytotrophoblast proliferation by activating the type-I IGF receptor (IGF1R) in first trimester human placenta. Ligand access to receptors is regulated by IGF binding proteins (IGFBPs) 1-6. In humans, the most abundant IGFBPs at the maternal-fetal interface are IGFBP-1 and IGFBP-3; we hypothesised that these IGFBPs function to regulate the effects of IGFs in the placenta and used our placental explant model, in which proliferation and differentiation are...

ea0028oc2.5 | Reproduction and bone | SFEBES2012

Nutrient regulation of growth factor signalling in human placenta

Nadif Raja , Sykioti Vasia , Aplin John , Westwood Melissa

The in utero environment is crucial for both the prenatal and long-term health of the offspring. The placenta is able to modify its structure/function in response to maternal growth and nutritional signals to actively regulate maternal-to-fetus nutrient transfer and consequently optimum fetal development. Little is known about the molecular mechanisms involved in placental sensing of maternal nutrients. However, we postulate that nutrient flux through the hexosamine biosynthet...

ea0028oc2.6 | Reproduction and bone | SFEBES2012

Identification of microRNAs involved in regulating growth factor signalling in the first trimester placenta

Farrokhnia Farkhondeh , Westwood Melissa , Aplin John , Forbes Karen

Fetal growth restriction and overgrowth (macrosomia) are both associated with altered placental development and problems at birth. Both conditions have lifelong impacts on health including an increased risk of developing cardiovascular disease and diabetes. Placental development depends on co-ordinated cellular growth and is enhanced by maternally-derived growth factors. MicroRNAs (miRs) are known to regulate gene expression and we have shown that global miR suppression in pla...

ea0025p205 | Growth and development | SFEBES2011

Identification of turner syndrome specific mRNA expression profiles that correlate with clinical response to growth hormone

Stevens Adam , Tajbakhsh Shahin , Whatmore Andrew , Westwood Melissa , Clayton Peter

Girls with Turner syndrome (TS) are treated with recombinant human growth hormone (rhGH) to improve their adult height but the gain is variable (0–20 cm). Current prediction models can account for only ~46% of the variability in the first year response to rhGH, thus genetic profiling has been suggested as a possible means of improving this prediction. The aim of this study was to explore mRNA expression profiles in an ex-vivo fibroblast model to characterise response to r...

ea0023oc1.2 | Oral Communications 1 | BSPED2009

Altered GH/IGF1 signalling in children born small for gestational age without catch up growth

Butcher Imogen , Whatmore Andrew , Murray Philip , Westwood Melissa , Clayton Peter

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. GH and IGF1 receptor mutations only account for a minority of cases. We have now initiated an in vitro assessment of signalling molecules downstream of these receptors and evaluation of cell growth characteristics.<p class="abstext"...

ea0021p227 | Growth and development | SFEBES2009

Altered responses to GH and IGF1 in children born small for gestational age without post-natal catch up growth

Butcher Imogen , Whatmore Andrew , Murray Philip , Westwood Melissa , Clayton Peter

Background: Infants born small for gestational age (SGA) usually show catch up growth within the first few years of life. However in the UK ~1500 SGA children each year remain small, with no clear endocrine cause with rare genetic syndromes accounting for only a minority of cases. In order to define growth factor activation in these children we have initiated an assessment of cell growth and signalling in response to GH and IGF1 in fibroblast cell lines....

ea0021p316 | Reproduction | SFEBES2009

The tyrosine phosphatase, SHP-1, acts on multiple tyrosine kinase receptors to negatively regulate human cytotrophoblast proliferation

Forbes Karen , Skinner Laura , Aplin John , Westwood Melissa

Pregnancy complications such as fetal growth restriction are associated with abnormal placental cell (cytotrophoblast) proliferation and apoptosis. Regulation of these events is unclear but recently we have used a placental explant model to demonstrate that IGFs influence cytotrophoblast kinetics and demonstrated that the protein tyrosine phosphatase (PTP) SHP-2 is required for IGF actions in the placenta. However, SHP-2 accounts for only 20% of total PTP activity, suggesting ...