Endocrine Abstracts

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.

Method: Skin biopsies were obtained with local ethics approval from healthy children (n=3) and SGA children without post-natal catch up growth (n=3). Fibroblasts were isolated and serum starved at sub-confluence for 24 h. Cells were then stimulated with IGF1 (100 ng/ml) or GH (200 ng/ml) for 0, 15 and 30 min. The expression and activation of the signalling molecules Stat5b, Akt and MAPK were assessed by western blotting using antibodies that recognise either the total or activated isoforms of these proteins. Cell growth was defined by cell counting and Brdu incorporation, and apoptosis by TUNEL staining.

Results: Stat5b, Akt and MAPK were present in cells from both control and SGA children. Stat5b activation was decreased in SGA cells when compared to controls however activation of MAPK appeared to be similar in these two cell types. A different pattern of IGF1 stimulated Akt phosphorylation was found and we have demonstrated that activation of Akt 2 occurs in SGA cells and not in control cells. Cell growth was not different between normal and SGA cell lines. However, apoptosis was significantly increased in SGA cells.

Conclusion: GH and IGF1 signalling pathways and rates of apoptosis appear to be altered in SGA children without post-natal catch up growth. This may be indicative of a causative factor for post-natal growth retardation, or a cellular response/compensatory mechanism to the retarded growth seen in these children.