title: Comparison of the effects of propylthiouracil and selenium deficiency on T3 production in the rat.
abstract: Selenium deficiency and propylthiouracil (PTU) treatment both decrease hepatic type I T4 5'-deiodinase activity (5'D-I), which is considered to be an important regulator of the serum T3 derived from peripheral T4 to T3 conversion (T3 neogenesis). The effects of PTU treatment or a selenium-deficient diet on T4 and T3 kinetics were compared in thyroid-ablated rats infused with stable T4 to determine whether PTU treatment is a more potent inhibitor of T3 neogenesis than selenium deficiency and to compare the degree of inhibition of T3 production with the degree of inhibition of 5'D-I. PTU treatment and selenium deficiency (Se-) did not affect the T3 MCR (control, 46.0 +/- 2.5; PTU, 41.7 +/- 2.8; Se-, 41.1 +/- 4.0 ml/h.100 g BW), but did reduce serum T3 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- vs. control) and the T3 production rate by 35% and 32%, respectively (control, 26.6 +/- 1.0; PTU, 17.3 +/- 2.0; Se-, 18.0 +/- 1.9 ng/h.100 g BW; P < 0.01 for PTU or Se- vs. Control). PTU treatment and selenium deficiency significantly increased serum T4 concentrations by 36% and 32%, respectively, due to a decrease in T4 MCR (control, 1.4 +/- 0.1; PTU, 1.1 +/- 0.1; Se-, 1.1 +/- 0.04 ml/h.100 g BW; P < 0.05 for PTU or Se- vs. control). Assuming that the concentration of T4 available for T3 neogenesis is proportional to the serum T4 concentration, the increase in serum T4 concentrations caused by PTU treatment or Se- would probably have proportionally increased the rate of T3 neogenesis. Based on these considerations, the apparent decrease in T3 neogenesis in the PTU-treated animals was 52%. This is less than the 79% and 67% inhibition of 5'D-I noted, respectively, in the liver and kidneys of these rats. Similarly, the apparent decrease in T3 neogenesis 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 suggest that PTU and Se- have similar effects on T3 neogenesis. The more potent effects of these treatments on liver and kidney 5'D-I activities than on T3 neogenesis suggest that the activities of these enzymes in these tissues are not the only important determinants of the serum T3 that is derived from nonthyroidal sources.
authors.affiliation: Division of Endocrinology and Metabolism, University of Massachusetts Medical School, Worcester 01655, USA.
authors.forename: I E
authors.initials: IE
authors.lastname: Veronikis
authors.forename: L E
authors.initials: LE
authors.lastname: Braverman
authors.forename: S
authors.initials: S
authors.lastname: Alex
authors.forename: S L
authors.initials: SL
authors.lastname: Fang
authors.forename: B
authors.initials: B
authors.lastname: Norvell
authors.forename: C H
authors.initials: CH
authors.lastname: Emerson
mesh_terms: D000818:Animals; D001835:Body Weight; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000172:deficiency*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000096:biosynthesis* / Q000097:blood
chemical_list: D004791:Enzyme Inhibitors; D014284:Triiodothyronine; D011441:Propylthiouracil; D013972:Thyrotropin; D007453:Iodide Peroxidase; D012643:Selenium; D013974:Thyroxine