Abstract

The purpose of the present study was to elucidate the mechanism by which thyroid hormone alters urea synthesis. The relative importance of urea cycle enzyme activities, substrate levels or the levels of urea cycle intermediates on urea production was investigated in a set of four experiments in which rats were fed a diet supplemented with 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) and treated with triiodothyronine (T3). Compared with that of normal or control rats, the plasma level of T3 was significantly lower in rats fed a diet containing PTU only and elevated in rats given PTU + T3. Urinary excretion of urea and the liver content of ornithine in rats given PTU + T3 were significantly lower than in rats given PTU only. The liver level of ornithine was closely correlated to the excretion of urea in the present study. Fractional rates of protein synthesis in liver, kidney and small intestine were lower in the hypothyroid group. However, most free amino acid concentrations, except ornithine in liver and plasma and the activity of hepatic argininosuccinate synthetase (EC 6.3.4.5) of hypothyroid rats, were significantly reduced as compared with those of control or hyperthyroid rats. The results indicate that the increased hepatic ornithine content in the hypothyroid rats may be one of the regulatory factors causing changes in urea synthesis.

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