Relative rates of tryptophan pyrrolase degradation following the administration of hydrocortisone and tryptophan to intact and adrenalectomized rats

Abstract

Studies have performed in normal and adrenalectomized rats to examine the mechanisms underlying hormonal and substrate induction of liver tryptophan pyrrolase (tryptophan oxidoreductase, EC 1.13.1.12). Tryptophan pyrrolase was induced either by the intraperitoneal administration of hydrocortisone sodium succinate or l-tryptophan. In a number of experiments actinomycin D was given to inhibit mRNA synthesis, in others puromycin dihydrochloride was given to prevent protein synthesis. After tryptophan administration to intact rats depression of enzyme degradation occurred (the t 1 2 for tryptophan pyrrolase after puromycin administration is significantly increased). Such a depression in the degradation of tryptophan pyrrolase was not observed during hormonal induction of the enzyme (in animals receiving hydrocortisone the t 1 2 for tryptophan pyrrolase following puromycin administration remained relatively constant). Actinomycin D had no effect on substrate induction of tryptophan pyrrolase in adrenalectomized animals. However, in intact animals the induction of tryptophan pyrrolase by substrate was greater than that observed in adrenalectomized animals, and this induction was significantly diminished by actinomycin D. Thus, based on present work and work reported in the literature, it appears that (1) hormonal induction of tryptophan pyrrolase in normal and adrenalectomized animals is associated with increased tryptophan pyrrolase synthesis which is dependent on new mRNA synthesis; (2) substrate induction of tryptophan pyrrolase in adrenalectomized animals is associated with decreased enzyme degradation; and (3) substrate induction in intact animals depends both upon decreased degradation of tryptophan pyrrolase and on an increased synthesis of the enzyme, which is dependent on new mRNA synthesis.