Role of thyroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoyl-phosphate synthase (ammonia) activity in axolotl liver

1. In axolotl liver, the activity of carbamoyl-phosphate synthase (ammonia), expressed per mg liver protein, decreases to a minimum at 5 months of age, then increases to a maximum at 8 months of age which is followed by a decrease again. The initial decrease between 3 and 5 months of age appears to be largely due to an increase in non-carbamoyl-phosphate synthase protein and the following increase between 5 and 8 months of age to a relative increase of carbamoyl-phosphate synthase protein. 2. Treatment of the animals with triiodothyronine causes an increase in carbamoyl-phosphate synthase activity, the extent of which is dependent upon hormone concentration and age of the animal. After 8 months of age no increase of enzyme occurs upon thyroid hormone treatment, although metamorphosis occurs. 3. Glucocorticosteroid hormones stimulate carbamoyl-phosphate synthase activity 2-to 3-fold in animals older than 6 months. However, in animals younger than 6 months, low concentrations of thyroid hormone, insufficient to induce metamorphosis, are necessary as permissive agents. 4. The stimulatory effects of high concentrations of thyroid hormones (T3) on carbamoyl-phosphate synthase appear to be mediated via a stimulatory effect on glucocorticosteroid biosynthesis. 5. The natural rise in enzyme activity between 5 and 8 months of age seems to be due to a rise in the concentration of circulating glucocorticosteroid hormones