Endocrine Abstracts

Objective: To assess age- and growth-dependent gene expression in children and correlate this with biological pathways.Methods: We conducted a gene expression meta-analysis on datasets from normal children curated from the NCBI Gene Expression Omnibus (GEO). Four datasets were combined to form a group of 87 individuals ranging from 0.2 to 29.3 years of age (average 7.7±6.9yr). Analysis of gene expression data was performed using hierarchical cluster...

Introduction: 3-M syndrome is associated with mutations in CUL7, OBSL1 and CCDC8 with the three proteins interacting within a novel growth pathway. The impact of this pathway on cellular growth has not been fully defined. We have shown that i) GH and IGF1 signalling are altered; ii) IGF2 expression is reduced and iii) expression of insulin receptor isoforms are altered in 3-M fibroblasts.Aim: To characterise the activa...

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...

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"...

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....

Good growth in children is associated with large, disordered, fluctuations in GH levels from week to week (Gill et al., 1999; Gill et al., 2001). However, GH treatment regimens are restricted to daily fixed doses which may not provide optimal growth. We have used GH-deficient dwarf rats (dw/dw) to test our hypothesis that variable GH dosing will enhance growth.Six week old, male dwarf rats (16 per group) were treated for 6 weeks with either...

Children diagnosed with either Growth Hormone deficiency (GHD) or Turner syndrome (TS) are both treated with GH titrated against either weight or area. The response to such treatment however, is highly variable and, at least in part, diagnosis dependent. The precise mechanisms underlying this variability are unknown. As basal GH levels differ between GHD and TS and, as GH elicits its effects through changes in gene expression, the basal gene expression profiles of GHD and TS s...

Background: Previous studies use small for gestational age (SGA) as a surrogate marker for fetal growth restriction (FGR). SGA individuals, particularly those who show catch-up growth have greater cardiometabolic (CM) risk than those born appropriate for gestational age. However, not all FGR fetuses are born SGA. Therefore, we studied neonates born following pregnancies at increased risk of FGR, irrespective of birthweight.Aim: To define associations bet...

Background: Cardiometabolic (CM) risk is linked to being small for gestational age (SGA, birthweight <-2SDS). Suboptimal fetal growth alone may be linked with greater CM risk without resulting in SGA. Therefore, we focused on CM risk in children born following pregnancies at higher risk for growth restriction, irrespective of birthweight.Aims: 1. To identify associations between fetal and childhood weight trajectories and CM risk markers. 2. To defin...

Cardiovascular risk factors are more prevalent in south Asian (SA) adults compared to White Europeans (WE), although the reasons for this are not fully known. Vascular growth factors (VGFs) are increasingly recognised to have various roles in arterial development, function and remodelling. We hypothesised that ethnic differences in VGFs in early life contribute to the later differences in CV risk. We further hypothesised that arterial stiffness, as a measure of large artery st...