Effects of Thiouracil and of Thyroidectomy on Liver Protein Metabolism

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Abstract
Incorporation of 0.5% thiouracil into an 18% casein diet for 21 days increased both relative (g/100 g body wt) and actual liver weights in mature male rats. However, thyroidectomy decreased liver weights below euthyroid control level. Thiouracil feeding increased protein/DNA ratios above controls; thyroidectomy decreased these ratios. The thiouracil-treated animals had RNA /DNA ratios equal to controls, whereas in thyroidectomized rats they were reduced. The halflives of liver cell protein fractions were estimated using 35S DL-methionine. Both thyroidectomy and thiouracil feeding increased the half-life of total liver protein and most subcellular fractions. However, 35S incorporation indicated that the livers of thyroidectomized rats were synthesizing protein more slowly, which accounts for the reduced liver size. These data suggest that thiouracil feeding for 21 days increases liver size by decreasing the rate of protein catabolism, while not altering the rate of synthesis. Reduced liver size in thyroidectomized rats appears to be associated with a slower rate of protein synthesis. Thyroxine replacement to thyroidectomized animals raised the RNA/DNA ratio to control level. Nevertheless, liver weight remained unchanged, suggesting that catabolism was enhanced more than anabolism. The mechanism of thiouracil’s action on protein biosynthesis in the liver appears to be extrathyroidal. (Endocrinology74: 878, 1964)

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