Endocrine Abstracts

The in utero environment is crucial for both the prenatal and long-term health of the offspring. The placenta is able to modify its structure/function in response to maternal growth and nutritional signals to actively regulate maternal-to-fetus nutrient transfer and consequently optimum fetal development. Little is known about the molecular mechanisms involved in placental sensing of maternal nutrients. However, we postulate that nutrient flux through the hexosamine biosynthet...

Fetal growth restriction and overgrowth (macrosomia) are both associated with altered placental development and problems at birth. Both conditions have lifelong impacts on health including an increased risk of developing cardiovascular disease and diabetes. Placental development depends on co-ordinated cellular growth and is enhanced by maternally-derived growth factors. MicroRNAs (miRs) are known to regulate gene expression and we have shown that global miR suppression in pla...

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....

Pregnancy complications such as fetal growth restriction are associated with abnormal placental cell (cytotrophoblast) proliferation and apoptosis. Regulation of these events is unclear but recently we have used a placental explant model to demonstrate that IGFs influence cytotrophoblast kinetics and demonstrated that the protein tyrosine phosphatase (PTP) SHP-2 is required for IGF actions in the placenta. However, SHP-2 accounts for only 20% of total PTP activity, suggesting ...

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...

Objective: Insulin-like growth factor-II (IGF-II), a critical regulator of placental development, enhances proliferation and survival of human cytotrophoblasts by signalling through the IGF-1 receptor (IGF-1R). Excess IGF-II binds to IGF-2R, which mediates its transport to the lysosomes for degradation. Although considered to act solely as an IGF-II clearance receptor, IGF-2R has been implicated in mediating IGF-II-stimulated migration and invasion in trophoblast. We therefore...

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...

Insulin-like growth factor (IGF-I) is an important signal for mammary gland development and epithelial cell survival. Following lactation, the mammary gland undergoes involution through extensive epithelial cell apoptosis and thus, the IGF-I survival signal must be inhibited. IGF actions are regulated by association with high affinity binding proteins (IGFBPs) and the aim of this study was to investigate the expression of IGFBPs during mouse mammary gland development to determ...