Endocrine Abstracts (2009) 19 P197

Altered IGF-I signalling in children born small for gestational age without catch up growth

I Butcher, A Whatmore, P Murray, M Westwood & P Clayton

University of Manchester, Manchester, UK.

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 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 IGF-I (100 ng/ml) for 0, 15 and 30 min. The expression and activation of the signalling molecules, Akt and MAPK, were assessed by western blotting using antibodies that recognise either the total or activated isoforms of these proteins.

Results: Akt and MAPK were present in cells from both control and SGA children. Activation of MAPK appeared to be similar in these two cell types, however analysis of Akt activation revealed a different pattern of IGF-I stimulated Akt phosphorylation in cells from normal compared to SGA children. Further investigations demonstrated that the different isoforms which are known to have different cellular functions, are differentially activated in cells from SGA children.

Conclusion: IGF-I signalling pathways 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.

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