The regulation of post-natal growth in sheep through the growth hormone - insulin-like growth factor axis

Abstract

The GH-IGF axis is one hormonal system which is considered to control muscle growth. To investigate the factors controlling post-natal growth of skeletal muscle in lambs, methods of histological autoradiography were developed in the experiments presented in this thesis to provide sensitive measurement of hormone binding in vitro to receptors. The techniques were used to measure receptors for GH, IGF1 and IGF2 in skeletal muscle of prepubertal lambs which had undergone treatment with exogenous growth factors and/or degrees of nutritional restriction before slaughter. Plasma concentrations of IGF1 were positively correlated with good nutrition and treatment of animals with exogenous GH. Whether or not the changes in plasma IGF1 concentrations are associated with changes in the binding of IGF1 to skeletal muscle is possibly dependent on the age of the animal, the severity of nutritional restriction and the tissue type in skeletal muscle from which measurements were taken. Binding of IGF1 was demonstrated in both the muscle fibre and connective tissue in lambs of six months old, with an increase of binding in connective tissue associated with fasting. In lambs of eight months old, binding was present only in connective tissue and not regulated by GH treatment or nutritional restriction of animals. Plasma concentrations of IGF2 were not altered with fasting of animals. Binding of IGF2 was restricted in distribution to connective tissue in six month old lambs and also insensitive to fasting. The greatest density of IGF1 and IGF2 binding in skeletal muscle was always observed associated with blood vessels. GH binding in skeletal muscle was not demonstrated. In conclusion, connective tissue appears to be a more sensitive target tissue than muscle fibre through which the IGFs may mediate the effects of changes in nutritional status.