The effect of cortisone upon protein synthesis.

For some time, it has been known that the injection of adrenal cortex extracts or adrenal steroids containing oxygen substitutions at the Cn position augments the excretion of nitrogen in the urine of animals either fasting or feeding normally. Similar injections into adrenalectomized or hypophysectomized animals also raise the fasting nitrogen excretion above normal (l-3). On the contrary, the loss of cortical secretion is accompanied by a decreased urinary nitrogen excretion (3-9). It was thought that finding the mechanism of the increased output of urinary nitrogen, following adrenal steroid therapy, might help to clarify the r&e of these steroids in protein metabolism. Cortisone (17+hydroxy11-dehydrocorticosterone) typically increases the urinary nitrogen excretion of rats and man. In 1942, Albright (10) suggested that the ll-oxygenated steroids perhaps were concerned with an antianabolic action rather than a catabolic one on protein. However, there are conflicting reports in the literature as to whether cortisone exerts this effect upon protein synthesis (11) or upon protein breakdown (12). The results obtained in the following experiments appear to confirm the Albright concept that one of the actions of the adrenal cortical hormone is to inhibit protein synthesis, although a lesser effect upon protein catabolism cannot be overlooked. When an amino acid is fed to an animal, it mixes with the other constituents of the metabolic pool and part of its nitrogen may be used for protein synthesis while another part is converted to excretory products. The more efficient the utilization of the amino acid for protein synthesis, the less of its nitrogen will be found in the urine. Recently, Sprinson and Rittenberg (13) have shown that, by feeding a tracer dose of an isotopic amino acid (X15-glycine) and by determining the amount of its nitrogen excreted in the urine, they could calculate the rate of protein synthesis. This technique has accordingly been employed in both normal and adrenalectomized rats, some of which had received cortisone, in an attempt to determine whether cortisone affected the rate of protein synthesis. Experiment l-White male rats of the Wistar st,rain were used. 1 month prior to their use, half had been adrenalectomized and a sham operation was performed on the other half. All animals received 1 per cent sodium chloride in their drinking water. The treated animals received 3 mg. of