Changes in Liver Concentration of N-Acetylglutamate and Ornithine are Involved in Regulating Urea Synthesis in Rats Treated with Thyroid Hormone

Abstract

The purpose of this study was to elucidate the mechanism by which thyroid hormone alters urea synthesis. A set of three experiments was investigated in three groups of rats given 6-propyl-2-thiouracil (a thyroid inhibitor) without triiodothyronine treatment, treated with 6-propyl-2-thiouracil plus triiodothyronine or neither 6-propyl-2-thiouracil nor triiodothyronine (control). We attempted to determine whether the concentration of ornithine and N-acetylglutamate regulated urea synthesis and whether activities of two ornithine-catabolizing enzymes accounted for changes in ornithine concentration. Urinary excretion of urea and the liver concentration of N-acetylglutamate and ornithine in rats given 6-propyl-2-thiouracil plus triiodothyronine were significantly lower than in rats given 6-propyl-2-thiouracil alone. The liver concentration of N-acetylglutamate was correlated to urea excretion (r = 0.911, P < 0.001). The activities of carbamylphosphate synthetase, ornithine aminotransferase and ornithine decarboxylase in liver of the group treated with 6-propyl-2-thiouracil alone were significantly lower than those of the 6-propyl-2-thiouracil plus triiodothyronine-treated group. The results suggest that a higher liver concentration of N-acetylglutamate and ornithine in the hypothyroid (6-propyl-2-thiouracil only) rats is likely to stimulate urea synthesis. The thyroid hormone-induced increase in activities of ornithine catabolizing enzymes may be primarily responsible for changes in ornithine concentration.