COMPARISON OF THE EFFECTS OF PROPYLTHIOURACIL AND SELENIUM DEFICIENCYON T-3 PRODUCTION IN THE RAT

Selenium deficiency and propylthiouracil (PTU) treatment both decrease hepatic type I T-4 5'-deiodinase activity (5'D-I), which is considere d to be an important regulator of the serum T-3 derived from periphera l T-4 to T-3 conversion (T-3 neogenesis). The effects of PTU treatment or a selenium-deficient diet on T-4 and T-3 kinetics were compared in thyroid-ablated rats infused with stable T-4 to determine whether PTU treatment is a more potent inhibitor of T-3 neogenesis than selenium deficiency and to compare the degree of inhibition of T-3 production w ith the degree of inhibition of 5'D-I. PTU treatment and selenium defi ciency (Se-) did not affect the T-3 MCR (control, 46.0 +/- 2.5; PTU, 4 1.7 +/- 2.8; Se+, 41.1 +/- 4.0 ml/h . 100 g BW), but did reduce serum T-3 concentrations by 29% and 25%, respectively (control, 58.7 +/- 2.6 ; PTU, 41.5 +/- 1.0; Se-, 43.9 +/- 2.7 ng/dl;P < 0.01 for PTU or Se- v s. control) and the T-3 production rate by 35% and 32%, respectively ( control, 26.6 +/- 1.0 for PTU or Se- vs. Control). PTU treatment and s elenium deficiency significantly increased serum T-4 concentrations by 36% and 32%, respectively, due to a decrease in T-4 MCR (control, 1.4 +/- 0.1; PTU, 1.1 +/- 0.1; Se-, 1.1 +/- 0.04 ml/h . 100 g BW; P < 0.0 5 for PTU or Se- vs. control). Assuming that the concentration of T-4 available for T-3 neogenesis is proportional to the serum T-4 concentr ation, the increase in serum T-4 concentrations caused by PTU treatmen t or Se- would probably have proportionally increased the rate T-3, ne ogenesis. Based on these considerations, the apparent decrease in T-3 neogenesis in the PTU-treated animals was 52%. This is less than the 7 9% and 67% inhibition of 5'D-I noted, respectively, in the liver and k idneys of these rats. Similarly, the apparent decrease in T-3 neogenes is in the Se- rats was 48%, again less than the 85% and 64% inhibition of 5'D-I in their liver and kidneys, respectively. These studies sugg est that PTU and Se- have similar effects on T-3 neogenesis. The more potent effects of these treatments on liver and kidney 5'D-I activitie s than on T-3 neogenesis suggest that the activities of these enzymes in these tissues are not the only important determinants of the serum T-3 that is derived from nonthyroidal sources.