Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of Nτ-methylhistidine

Abstract

The role of glucocorticoids in regulating the rate of muscle protein breakdown was evaluated by measuring excretion of N.tau.-methylhistidine during administration of various doses of corticosterone to adrenalectomized rats. Groups of rats received daily s.c. injections of 0, 0.2, 0.5, 1.0, 5.0 or 10.0 mg of corticosterone/day per 100 g body weight for 7 days, followed by 3 days without hormone treatment, after which they were killed. A group with intact adrenal glands served as an additional control. All animals were pair-fed with the untreated adrenalectomized group. No significant differences were noted in growth rate or N.tau.-methylhistidine excretion between the intact or adrenalectomized control groups, or those given 0.2, 0.5 and 1.0 mg of corticosterone, whereas growth ceased and N.tau.-methylhistidine excretion rose markedly in the groups receiving 5 and 10 mg of corticosterone. After these 2 high doses of corticosterone, but not after lower doses, there was a loss of weight of the gastrocnemius muscle per 100 g of final body weight, but not of the soleus and extensor digitorum longus muscles. The 2 highest doses of corticosterone also resulted in an increase in liver weight/100 g of final body weight. Lower doses of corticosterone did not cause these changes. Plasma corticosterone concentrations, measured on the final day of injection and again at the time of killing, were decreased to near 0 by adrenalectomy and were only slightly raised by doses of 0.2 and 0.5 mg daily, but were increased to within the normal range by the 1 mg dose. At 5 and 10 mg doses, plasma corticosterone concentrations were sustained at 2-3 times those of intact rats, and thus in the range reported for rats exposed to severe stress. Rats given 5 and 10 mg doses of corticosterone had glycosuria, and showed considerably elevated concentrations of insulin in the plasma. Plasma concentrations of glucocorticoids within the normal range do not regulate the rate of muscle protein breakdown, whereas excessive plasma concentrations of corticosteroids, equivalent to those observed in severe stress, can accelerate muscle protein breakdown.