Molecular Pharmacology, Vol 18, 247-252, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Ornithine Decarboxylase Activity in the Developing Heart of Euthyroid or Hyperthyroid Rats

¹ Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710

Ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, displays high activity early in postnatal development of the heart, followed by a gradual decline to the low levels characteristic of adults. In both 2- and 4-day-old rat pups, kinetic studies revealed the presence of two distinctK_m^orn values of 50-60 and about 250 µM. However, by 7 days of age, only one form of the enzyme could be detected, with a K_m^orn of 200-250 µM; after this point, the K_m^orn remained at the low-affinity value, and further age-dependent reductions in activity occurred due to a progressive decline in the V_max. The rate of disappearance of ODC activity, measured after the administration of cycloheximide, did not change with age. Neonatal administration of triiodothyronine (T₃) evoked an initial elevation of ODC followed by depressed activity. As was true of controls, ODC from 2-day-old T₃-treated rats displayed two separate kinetic forms, but the V_max values of both forms were elevated above those of controls. At 10 days of age, only lowaffinity ODC could be found in T₃-treated rats, and the V_max was below that of controls. Cycloheximide treatment revealed only small changes in the half-life of ODC activity after T₃ treatment. The accelerated maturational decline of cardiac ODC in hyperthyroid rats was correlated with depressed RNA synthesis and with subsequent deficits in heart weight. These results indicate that the developmental decline of heart ODC can be explained by the disappearance of the high-affinity kinetic form of the enzyme as well as by a reduction in enzyme synthesis and/or catalytic efficiency; after its initial stimulatory effect, neonatal hyperthyroidism exerts a deleterious effect on ODC activity which may contribute to deficient nucleic acid synthesis and cardiac growth.