Role of glucocorticoids in increased muscle glutamine production in starvation

The influence of glucocorticoids on muscle glutamine production in starvation was studied by using cortisol-treated or non-cortisol-treated, starved, adrenalectomized rats. Administration of cortisol at physiological doses in vivo (1 mg/100 g body weight) to fasted, adrenalectomized rats increased the muscle ratio of glutamine/glutamate and the activity of glutamine synthetase after only 6 hours. Prior treatment of fasted, adrenalectomized animals with actinomycin D or proflavine abolished these increases by cortisol. Therefore, cortisol induces muscle glutamine synthetase, and this induction can be detected by changes in the fresh-muscle ratio of glutamine/glutamate. Using this ratio as a qualitative indicator of muscle glutamine synthesis, the role of glucocorticoids in modifying muscle glutamine production in starvation was studied. In fresh-frozen soleus, extensor digitorum longus, and diaphragm muscle, starvation led to greater ratios of glutamine/glutamate and higher levels of tyrosine, which are indicative of enhanced muscle protein turnover. These effects were not apparent in starved, adrenalectomized animals but were restored, at least partially, by administering a physiological dose of cortisol. Therefore, glucocorticoids seem essential for promoting muscle glutamine production in starvation probably by inducing the activity of glutamine synthetase.