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...

Gene arrays are a powerful tool to search for novel targets of drug action and disease-specific patterns of gene expression. GH has pleiotropic actions and thus a wide range of potential gene targets. Using an accessible tissue, namely peripheral blood mononuclear cells (PBMNCs), we have started to explore the use of gene arrays in the context of the in-vivo response to GH treatment.PBMNCs were obtained with consent and ethical permission from 2 prepuber...

Ghrelin, a novel GH-releasing n-octanoylated peptide, has been identified as an endogenous ligand for the 'orphan' GH secretagogue receptor. When administered iv or icv, Ghrelin causes a greater increase in serum GH concentrations than hexarelin or GHRH. However Ghrelin has a number of other actions: it promotes food intake, raises serum glucose and inhibits insulin secretion, increases ACTH and cortisol secretion and influences cardiac function.In orde...

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....

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. IGF-I receptor mutations account for a minority of cases therefore we have initiated an assessment of signalling molecules downstream of the receptor.Method: Skin biopsies were obtained with local ethics approval from he...

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...