Growth hormone antagonizes the induction of tryptophan pyrrolase and tyrosine aminotransferase by cortisol. We have shown that, contrary to previous reports, growth hormone is also capable of antagonizing the induction of these enzymes by tryptophan and α-methyl tryptophan. As α-methyl tryptophan is not metabolized appreciably in the rat, our data show that growth hormone does not act indirectly through changes in the liver tryptophan content as was suggested previously. Growth hormone decreases the rate of tryptophan catabolism in vivo after induction of tryptophan pyrrolase by tryptophan and α-methyl tryptophan. Because the rate of catabolism of a tryptophan load is slower in animals treated with growth hormone, tissue tryptophan levels and the rate of synthesis of 5-hydroxytryptamine in the brain are higher in these animals than in those receiving tryptophan alone. Thus, although tryptophan administration raises brain 5-hydroxytryptamine levels, induction of tryptophan pyrrolase in the liver, by the load, limits the extent and duration of the rise in brain 5-hydroxytryptamine synthesis. This has important implications for the clinical use of tryptophan in psychiatric disorders, where tryptophan is given to produce long-lasting elevations of brain 5-hydroxytryptamine.
MECHANISM OF DECLINE IN RAT BRAIN 5-HYDROXYTRYPTAMINE AFTER INDUCTION OF LIVER TRYPTOPHAN PYRROLASE BY HYDROCORTISONE: ROLES OF TRYPTOPHAN CATABOLISM AND KYNURENINE SYNTHESIS