ESPE Abstracts

Introduction: Growth promoting effects of GH occur in parallel with its impact on insulin sensitivity and lipid metabolism; underlying biological networks that link these actions are not defined. Our objective was to identify gene expression (GE) networks linking growth with metabolic responses in GH-treated children with GHD.Methods/design: Pre-pubertal children with GH Deficiency GHD (n=125) were enrolled from the PREDICT short-term (NCT002561...

Background: GRB10 negatively regulates IGF1 signalling, influences growth and promoter polymorphisms are associated with GH response1. GRB10 knockout-mouse models display foetal overgrowth2, however, the mouse model has only partial similarity to human growth3. There is evidence that the zebrafish is an appropriate model to study growth4 and has the advantage of being easily genetically manipulated.<p class="abs...

Background: The phases of human growth are associated with gene expression (GE) changes1, raising the possibility that rhythmic patterns of GE occur throughout childhood.Objective: In this study, we have assessed time-series patterns of GE profiles associated with age to characterise oscillations.Methods: GE analysis was conducted on cells of lymphoid origin from normal individuals through childhood (n=87, 43 ma...

Background: GH response is influenced by genetic polymorphisms, including the rs1024531 polymorphism (A/G) in the promoter region of GRB10, a negative regulator of signaling through the IGF1 receptor. Allele A is associated with borderline lower baseline IGF1 SDS and 1.5-fold higher response to GH compared to allele G in children with GHD (P=0.0006).Objective: To test functional impact of the rs1024531 polymorphism in an in vitro</e...

Introduction: Genetic markers associated with the response to recombinant human GH (r-hGH) have been identified in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) children in the PREDICT long-term follow-up (LTFU) prospective study (NCT00699855).1 A validation (VAL) study (NCT01419249) was conducted to confirm association.Methods/design: Inclusion criteria for GHD and TS children were identical in the LTFU and VAL studies (GHD defined...

Background: Response to GH treatment has been associated with single nucleotide polymorphisms (SNPs) within the promoter region of growth-related genes including GRB10 (rs1024531 (A/G, allele A increased response)), IGFBP3 (rs3110697 (G/A, G increased response)), CYP19A1 (rs10459592 (T/C, T increased response)) and SOS1 (rs2888586 (G/C, C increased response)). SOS1 is a positive regulator of GH signalling (MAPK pathway); the aromatase CYP19A1 promotes oestrogen synthesis to im...

Background: Obese adults with normal glucose tolerance (NGT) but 1-h post load glucose (1 hPG)≧155 mg/dl have an increased cardiometabolic risk. In children, preliminary data suggest that 1hPG≧132.5 mg/dl might identify those at higher risk of type 2 diabetes.Objective and hypotheses: To assess whether NGT obese youth with 1hPG ≧132.5 mg/dl (High-NGT) have worse insulin sensitivity and secretion compared to obese youth with 1hPG &#60...

Background: In humans GRB10 negatively regulates GH and IGF1 signaling predominantly via altering phosphorylation of PI3K/mTOR/AKT and MEK/ERK pathways which relate to both growth and metabolic function. We have previously shown that Grb10 knockdown in Zebrafish results in overgrowth with an increase in length and head size. However the impact on weight in relation to length has not been assessed.Objective: To develop a model t...

Background: Controversial data exist on the possibility that inhaled glucocorticoids (IGs) affect growth in children with mild-to-moderate asthma. The majority of these studies are short-term reports lacking long-term assessment until the achievement of final height (FH).Objectives: To assess whether IGs affect growth and FH in asthmatic children compared to controls.Methods: 113 asthmatic (57/56 (males/females)) were compared to 6...

The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis encapsulates the relationship between pre- and perinatal exposures causing altered growth and the development of later life disease. Mediators of this relationship have not been fully defined. We have used zebrafish [ZF] (Danio rerio) as a potential model for DOHaD, modifying expression of grb10a, an adapter protein that interacts with the insulin and IGF receptors, to act as a negative r...