The independence of hydrocortisone and tryptophan inductions of tryptophan pyrrolase.

The activity of the mammalian liver tryptophan pyrrolase (peroxidase-oxidase) (1) was greatly increased after the injections of tryptophan (2). It was later found that increased liver enzyme levels could be produced by various stressing conditions and by injection of such substances as histidine and tyrosine (3) and histamine and adrenaline (4) in intact animals, and by adrenocorticotropic hormone (5) and the glucocorticoid hormones (6,7), as well as tryptophan in adrenalectomized animals. These experiments indicated that there were two types of inducing agents, the substrate and an adrenal hormone, and that the enzyme could be induced in adrenalectomized rats by the substrate independently of the hormone. It remained to be determined whether the hormonal induction was brought about independently of the substrate concentration or secondary to an increase in the level of tryptophan in the tissues produced by the glucocorticoid hormones. The glucocorticoid hormones cause increased protein breakdown in the rat (S), with increased free amino acid levels in muscle, kidney, and liver (9, 10). Independence of the substrate and hormonal inductions was implicit in the findings that the effect of hydrocortisone on the enzyme level was enhanced in hypophysectomized rats, while that of tryptophan was decreased (6, 11). Better evidence was needed in this identification of a hormone as a direct inducer of an enzyme, because of the possible importance of this as a way for hormones to act in biological systems. Therefore, the free tryptophan levels in blood and liver and the excretion of tryptophan metabolites in the urine during induction of the enzyme by tryptophan and by hydrocortisone were determined. The additive effects of tryptophan and hydrocortisone given simultaneously to adrenalectomized rats, and the comparative actions of these inducers on enzyme formation in liver slices were also determined. The results indicated that hydrocortisone was a primary inducer of the enzyme which acted independently of the tryptophan concentration in the cells. Preliminary reports of this work have appeared (12-15).