Cortisone-provoked depression of plasma tyrosine concentration: relation to enzyme induction in man.

Within 5 hours after administration of cortico-steroids to experimental animals, the activity of hepatic tyrosine-a-ketoglutarate transaminase is increased five-to tenfold (1-8). This enzyme cata-lyzes the initial step in tyrosine degradation and is one of several mammalian enzymes the activity of which is rapidly and substantially elevated by corticosteroids (9). Adrenal steroids also depress the concentration of tyrosine in plasma (10-11). The reduced level of tyrosine in plasma has been attributed to the increased hepatic activity of ty-rosine transaminase, i.e., an increased rate of degradation of tyrosine by the enzyme would be expected to diminish the plasma concentrations of the amino acid (10). The thyroid status of the animal has been recently shown to modify the typical corticosteroid-induced elevations of hepatic tyrosine transaminase activity. Massive amounts of hydrocortisone are required to elevate enzyme activity in thyroxine-treated rats, whereas in hypothyroid rats, even a small dose of hydrocortisone elevates enzyme activity maximally (12). Thyroxine, in further contrast to adrenal corticosteroids, produces elevations of the plasma level of tyrosine, and thyroidec-tomy decreases the concentration of tyrosine in plasma (13, 14). Despite extensive investigations of the alterations in the activity of tyrosine transaminase in experimental animals, only limited attention has * been paid to the possible existence of steroid-in-ducible enzymes in man. It is known from analyses of specimens of human liver that the pathway of tyrosine oxidation proceeds by the same sequence of reactions as in animal liver, and that the human tyrosine-a-ketoglutarate transaminase has properties similar to those of the animal enzyme (15, 16). It seemed likely, therefore, that the responses of the human transaminase to hormonal stimulation would also be similar to those described in animal liver. The finding in patients with thyrotoxicosis, as well as in thyroxine-treated animals, of increased concentrations of tyrosine in plasma (17-19) suggested a means of investigating the inducibility of the tyrosine transaminase system in man. Experiments were conducted to determine whether cortisone administration depresses the concentration of tyrosine in plasma of normal adult subjects , and secondly, whether cortisone has greater or lesser effects in patients with abnormal thyroid function. If enzyme induction were being modified by thyroid hormone, then subjects with hy-perthyroidism and myxedema should differ from euthyroid subjects in their responses to cortisone. Measurements were therefore made of tyrosine concentrations in plasma of hyperthyroid, euthy-roid, and hypothyroid subjects after an overnight fast and 3 hours after ingestion of a standard quantity of tyrosine.