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...

Background: Neanderthals split from an ancestral human population ~500,000 years ago and lived in Eurasia until 40,000 years ago. Early modern humans emerged in Africa ~350,000 years ago migrating into Eurasia 50,000 years ago. Interbreeding occurred between early modern humans and Neanderthals leading to the introduction of Neanderthal DNA into the early human population, a process termed introgression. In modern Eurasian populations around 2-4% of DNA is of Neanderthal origi...

Background: Recombinant human growth hormone (r-hGH) is the primary therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). There is a high cost associated with treatment and existing methods to predict response (and hence alter management) can only account for 40–60% of the variance.Methods: GHD (n=71) and TS patients (n=43) were recruited as part of a study (PREDICT) on the lo...

Background: The return to active long bone growth in puberty is a distinctly human event1 and occurs ~2 years earlier in girls compared to boys. Evolutionarily conserved networks of genes are associated with the developmental phases of childhood in multiple tissues2, implying the existence of a genetic program that controls the pubertal return to growth.Objectives: To identify biological functions associated with gender and age-rela...

Introduction: Growth rate tends to be greater in children living at higher latitudes although the underlying mechanisms are unclear. The aim of this study was to compare height velocity (HV) in response to recombinant human GH (r-hGH) therapy in children with GH deficiency (GHD) living at different latitudes.Design: Pre-pubertal children with GHD (n=118) were enrolled from the PREDICT long-term follow-up prospective study (NCT00699855). Data wer...

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: 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...

Background: GH deficiency (GHD) has a spectrum of severity as characterised by GH stimulation tests; the cut-off level for GHD has been a long standing contentious issue. An independent biological correlate of severity would be valuable.Objectives: To identify patterns of gene expression (GE) that correlate with severity in GHD.Methods: Pre-pubertal children with GHD (n=72) were enrolled from the PREDICT study (NCT00256126...

Maternal programming increases the risk of alterations in the offspring’s HPA axis. Previously we showed that maternal undernutrition in sheep induces epigenetic changes in the glucocorticoid receptors (GR) within hypothalamic energy balance pathways, without affecting HPA axis GR. However, these studies focussed on fetal tissues1. Here, we investigated whether GR is epigenetically altered in the HPA axis of adult offspring to determine the status of the pathwa...