The application of cytochemical procedures to characterize cell responses to growth hormone on skeletal muscle
Although human growth hormone has been available since 1956, little is known of its somatotrophic action on muscle, despite the fact that muscle constitutes a large proportion of the body's mass and is closely involved in growth. The present study was set up to investigate the effects of human growth hormone on the muscle of normal, intact and hypopituitary rat models. Changes were seen in the proportion of type 1 and type 2 fibres in the rat skeletal muscle 8 days after hypophysectomy, and after 7 days of growth hormone injection in both intact and hypophysectomised rats. Cytochemical analysis of myosin ATPase and succinate dehydrogenase activities in sections of rat hind limb muscles revealed that hypophysectomy reduced the proportion of type 1 fibres. This reduction was accompanied by the appearance of transitional (type 2C/1B) fibres in the extensor digitorum longus (EDL) muscle. Daily injection of human growth hormone led to an increase in the number of type 1 fibres in the EDL of young, adolescent and adult normal rats and in the EDL and soleus muscles of hypophysectomised rats. Eleven injections were sufficient to convert the majority of the transitional fibres in the EDL of the hypophysectomised rat back to type 1 fibres. These changes were accompanied by an increase in the number of myonuclei and satellite cells and by hypertrophy of type 1 and atrophy of type 2 fibres. Specificity studies showed that only growth hormone was able to elicit the above effects. These alterations in muscle fibre type occurred more rapidly than the changes in fibre type which are reported to take place after prolonged electrical stimulation of the muscle, or following extended periods of exercise. The findings reported in this thesis suggest that hypophysectomy and growth hormone injection can both result in alterations in the fibre type composition of skeletal muscle, which may have important implications for the muscles' speed of contraction and resistance to fatigue.