The effects of cortisone treatment on the protein turnover of the soleus muscle after immobilization.

Abstract

The glucocorticoid hormones appear to play an important role in mobilizing body proteins to facilitate gluconeogenesis in response to falling concentrations of plasma glucose. It has previously been shown (Goldberg & Goodman, 1969) that denervated skeletal muscle is more susceptible to the catabolic effects of cortisone. However, denervation is a rather drastic means by which to render a muscle inactive. In addition t o the deprivation of possible neurochemical influences, the presence of spontaneous electrical activity (Thesleff, 1963) and possible increased passive stretching of the tissue (Sola et al., 1973; Goldspink, 1978) make the denervated preparation a complicated system for studying inactivity. In the present investigation we have rendered the soleus muscle of young rats (approx. 40g pre-operatively, CD strain, Charles River U.K. Ltd.) inactive without depriving the muscle of its innervation. This was achieved by placing a plaster-of-Paris cast around the ankle joint of one hind limb. With thefoot restrained in the extended position the soleus muscle was immobilized in a fully shortened and unstretched state (Goldspink, 1977). We then examined changes in the size and protein turnover of the soleus muscle after 4 days of such immobilization. The changes in these NaCI-injected animals were compared with those in similar animals that had received two injections of cortisone acetate (0.25mg/day per lOOg body wt.) on each of the 4 days of immobilization. With this less complicated system, we re-examined the question of whether contractile activity protects muscle from the actions of catabolic hormones. In addition we have attempted to elucidate some of the mechanisms involved in such a response. The excess cortisone did not affect the growth rate of these young rats, as evidenced by similar increases in the body weights (approx. 2g/day) of both NaC1-treated and hormone-treated animals. Immobilization of the soleus muscle caused a significant decrease in the size of the tissue, compared with non-restrained controls (Table 1). These findings are in excellent agreement with a previous study (Goldspink, 1977), where it was shown that the immobilized soleus in such young rats undergoes a true atrophy and not simply decreased rates of growth. Since protein remained 16-17% of the muscle mass, changes in total protein closely paralleled the changes in muscle weight after immobilization (Table 1) . The presence of cortisone did not, however, appear t o have any additional influence on the weight of the immobilized muscle, nor indeed on the internal, non-restrained controls (Table 1). However, after cortisone treatment the protein composition fell to only 12% of the wet weight. Hence in the presence of excess cortisone, there was some fluid retention (Forsham, 1968) contributing to the unchanged wet weight of the immobilized tissue. This latter finding was not, however, true in the case of the control tissue on exposure to the hormone. So although cortisone had not affected the wet weight of the immobilized muscle, it had caused a greater net loss of protein (Table 1). Average rates of protein synthesis and protein breakdown were measured in vitro by the slightly modified method (Goldspink, 1978) of Fulks et al. (1975) to explain the changes in protein concentrations after immobilization, in the presence or absence of cortisone. Immobilization in the absence of excess hormone caused both a significant decrease in protein synthesis and an increase in protein degradation (Table 1). Thesecomplemen-