Endocrine Abstracts (2004) 7 P15

Growth retardation following prenatal GC exposure is more pronounced in the female offspring and is associated with raised serum IGF-1

T Mushtaq1, C Farquharson1, M Nyirenda2, E Seawright1, J Seckl2 & SF Ahmed3

1Bone Biology Group, Roslin Institute, Edinburgh, UK; 2Endocrinology Unit, Edinburgh University, Western General Hospital, Edinburgh, UK; 3Bone and Endocrine Research Group, Royal Hospital For Sick Children, Glasgow, UK.

Background: GCs retard growth prenatally in many mammals. Little is known of the prenatal effects of GCs in mice though this species is optimal for genetic and transgenic studies. IGFBP-2 is the predominant prenatal IGF binding protein and it may influence IGF action.

Aim: To determine the weights, crown rump lengths (CRL) and serum IGF-I, Insulin and IGFBP-2 levels on 1 day old mice exposed to GC prenatally.

Methods: Pregnant mice were exposed to Dexamethasone (Dex) (100microgramsg/kg/d) for the last 6 days of pregnancy. Controls received vehicle injections. The CRL and body weight were determined in 1 day old mice (n=90). A sub-set of these mice (control:Dex, 1:1) were injected with bromodeoxyuridine 1 hour before sacrifice, when blood was sampled and tibial length determined. Histological sections of tibiae were assessed for growth plate width and the chondrocyte proliferation rate.

Results: Dex treatment significantly decreased both body weight (11%; p<0.001) and CRL (7%;p<0.001). Female mice were more severely affected; body weight 16% decrease: (males 7%) and CRL 9% decrease (males 6%). There was a strong relationship between body weight and tibial length (r = 0.7, p<0.001). Median (10, 90 centile) serum IGF-I and IGFBP-2 in the prenatal Dex treated groups were higher at 291ng/ml (282, 297) and 3190ng/ml (3001, 3204) (p<0.05) than the control group; serum insulin was unaltered. A significant negative association was found between serum IGF-I and CRL (r = 0.5, p<0.03). There were no significant differences in the number of proliferating chondrocytes within the growth plate or the width of the proliferating and hypertrophic zones.

Conclusion: Prenatal GC exposure reduces birth weight and length; this effect is more marked in the female offspring and is associated with raised IGF-I and IGFBP-2 levels raising the possibility of a state of IGF-I insensitivity.

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