ESPE Abstracts

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...

Objective: Hospitalization in pediatric intensive care unit due to critical illness may be life threatening condition associated with severe acute physical stress and concomitant hormonal changes. Whether these changes represent an adaptive response or need to be treated is still not known.Methods: Pituitary hormones evaluation in four patients who were hospitalized in pediatric intensive care unit due to different sever...

Background: Low stress resilience in late adolescence and psychosocial traumatic events in adulthood have been linked to a higher risk of developing type 2 diabetes (T2DM) later on in life. However, limited data is available regarding whether prior stressors are related to the risk of developing T2DM in adolescence.Objective: We sought to determine the potential association between prior toxic stressors and T2DM in adolescence.Desi...

Background: The diagnosis of Growth Hormone Deficiency (GHD) involves the use of GH stimulation tests that require day case admission, multiple blood sampling and are associated with significant adverse effects.Aim: To assess the utility of gene expression (GE) profiling and candidate SNP analysis for the diagnosis of and classification of GHD.Method: Pre-pubertal treatment-naïve children with GHD (n=98) were enrolled from the...

Background: Single nucleotide polymorphisms (SNPs) within the promotor and 5’UTR of the transcriptional factor, ZBTB38, are associated with adult height and idiopathic short stature although their precise auxological effects have not previously been described. In addition, the molecular mechanisms through which ZBTB38 affects growth have not been fully elucidated but potential downstream mediators are suggested to include MCM10 or IGF2.Objectives: <...

Background: The relationship of pre-treatment gene expression (GE) to long-term growth response in GHD is unknown. Prediction of long-term response to r-hGH therapy would allow better decision making about start and maintenance doses and hence cost:benefit.Objective and hypotheses: To assess the relationship of baseline GE to response to r-hGH over 5 years of therapy in GHD children.Method: Pre-pubertal children with GHD (n</em...

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: 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...

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...

Growth response to daily GH treatment can be predicted using pre-treatment gene expression profiles.1 Once-weekly GH treatment potentially reduces the burden of daily injections2 and thus may be a major advancement in care for patients with GHD, vs standard, daily GH treatment. Here we investigate the prediction of first-year growth response based on pre-treatment blood transcriptome in children with GHD undergoing treatment with daily or once-weekly GH. ...