Effect of thyroid hormones on urea biosynthesis and related processes in rat liver

The results of the few studies on the effect of the thyroid status on nitrogen metabolism have been inconclusive and/or contradictory. In an attempt to elucidate this important relationship, we have studied the effect of experimental hypo- and hyperthyroidism on urea biosynthesis and related processes. We have found that the capacity of the liver to synthesize urea was increased in hypothyroid rats, as were the activities of the urea cycle enzymes; there were also changes in the activities of some related enzymes and in the levels of intermediates and amino acids. Isolated hepatocytes from these rats showed an increased capacity for urea synthesis. In hyperthyroid rats the picture was more complicated, since there was no change in the urea-synthesizing capacity of the liver, although there were changes in some enzymes and metabolites. Our results suggest that there may be more endogenous proteolysis in hypothyroidism which would increase ammonia production, the ammonia being used primarily for urea biosynthesis and, to a lesser extent, for glutamate and aspartate synthesis. These overall effects might be the result of an increase in glucagon and/or cAMP, which, as is well known, increase the urea-synthesizing capacity of liver. In hyperthyroidism, on the other hand, the changes in nitrogen metabolism could be the result of an increase in protein synthesis, a decrease in catabolic activity, or both.