HEPATIC AMINO NITROGEN CONVERSION AND ORGAN N-CONTENTS IN HYPOTHYROIDISM, WITH THYROXINE REPLACEMENT, AND IN HYPERTHYROID RATS

Background/Aims: The role of thyroid hormones in the regulation of hep atic conversion of amino nitrogen to urea is unresolved. The present s tudy was designed to assess ureagenesis in rats with experimentally we ll-established hypo- and hyperthyroidism. The possible role of propylt hiuracil (PTU), used for induction of hypothyroidism, was ascertained during thyroxine replacement of PTU treated hypothyroid rats. Methods: Basal blood amino nitrogen concentrations (AAN), the urea nitrogen sy nthesis rate (UNSR) and the maximal hepatic capacity for urea nitrogen synthesis (CUNS) obtained during alanine infusion were determined tog ether with N-contents in the soleus muscle and kidneys in experimental ly hypothyroid rats (n=19), upon thyroxine replacement (n=14) and in e xperimentally hyperthyroid rats (n=19). Hypothyroidism was induced by adding propylthiouracil (0.05%) to the drinking water for 5 weeks. Hyp erthyroidism was induced by thyroxine 100 mu g/100 g body weight. Resu lts: During hyperthyroidism, T-3 fell to less than 10%, food intake wa s halved, and body weight fell by 13%. Basal blood AAN fell by 25% (p< 0.01), UNSR more than doubled (p<0.01), and CUNS rose by 45% (p<0.05). N-contents of the soleus muscle fell by 13% and by 20% in kidneys, re spectively (p<0.05). Thyroxine replacement normalized AAN, UNSR, CUNS and reduced N-loss to 7% in the soleus muscle (NS) and kidneys (p<0.05 ), respectively. During hyperthyroidism, T-3 rose five-fold, food inta ke rose by two thirds, and body weight fell by 10%. Basal AAN rose by 20% (p<0.05), UNSR doubled (p<0.01), and CUNS rose by 25% (p<0.05). N- contents of the soleus muscle decreased by 19%, whereas kidney N-conte nts increased by 25% (p<0.05). Overall liver function assessed by gala ctose elimination capacity did not differ among groups. Both condition s increased the rate of urea synthesis; in the hypothyroid state the h epatic waste of amino-N was limited by low blood concentration of amin o-N, probably due to lower proteolysis. In the hyperthyroid state hepa tic amino-N loss was aggravated by higher blood concentration of amino -N, probably due to higher proteolysis. This difference may explain th e markedly different dietary nitrogen economy between the two groups. Conclusions: The findings suggest that distinct hepatic acceleration o f urea synthesis may contribute to the protein loss seen in both myxed ema and in thyrotoxicosis in humans.