Dietary Modification of Thyroxine Deiodination
نویسندگان
چکیده
on analysis of tissue from rats fed GC. Despite the clearcut (P < 0.01) increase in hepatic NP-SH and GSH conseqtuent to GC feeding, there was no alteration in iodothyronine deiodination compared to the group fed glucose alone. These data indicate that the effects of diet on T4 monodeiodination in liver are not mediated by changes in the tissue level of sulfhydryl compounds but rather involve alterations in the concentrations of the deiodinases. Received for puiblication 11 December 1979 and in revised form 21 January 1980. INTRODUCTION Caloric intake appears to be a major physiological regulator of thyroid hormone activation. It has been demonstrated that both short-term fasting (1) and longterm starvation (2-4) significantly depress the circulating levels of 3,5,3'-triiodothyronine (T3)' and elevate 3,3',5'-triiodothyronine (reverse-T3; rT3) in man. In man these dietary induced changes in thyroxine (T4) deiodination are a consequence ofa decrease in the daily production of T3 and in the disposal of rT3 (2-4). Tissue studies in animals, particularly in the rat liver, tend to support these in vivo findings (5, 6). The actual mechanisms by which fasting induces these changes have not been fully elucidated. Previous reports suggest that the effects of fasting result from a change in the concentration of deiodinase (7, 8) and/or in the availability of a cofactor (9, 10). T4 deiodination is thiol dependent (11) and, as the tissue (hepatic) levels of nonprotein sulfhydryls (NP-SH) and reduced glutathione (GSH) are diminished in the fasted state (9), it has been proposed that the effect of fasting is mediated throuigh a deficiency of these cofactors. It has been demonstrated that the effects of fasting on T4 deiodination to T3 can be reversed with the addition ofan excess ofthiol reagents in vitro (9, 10). However, we and others have failed to induce this reversal of the fasting effect (7, 8). To test the importance of tissue (hepatic) thiol content in the modulation of T4 deiodination consequent to dietary modification, we examined the deiodinatino of T4 to T3 and rT3 in liver homogenate from rats fed a variety of diets or fasted for the same period. The specific activity of each reaction was compared to 'Abbreviations used in this paper: F, fasted animals; G, animals fed 20% glucose in H20; GC, animals fed gluicose plus levels of cysteine increasing from 0.25%, G,, to 0.5%, GC2, and finally to 0.75%, Gc3; GSH, reduced glutathione; NP-SH, nonprotein sulfhydryls; P, Purina-fed controls; T4, thyroxine; T3, 3,5,3'-triiodothyronine; rT3, 3,3',5'-triodothyronine. J. Clin. Invest. ( The American Society for Clinical Investigation, Inc. 0021-9738/80/04/0943/04 $1.00 Volume 65 April 1980 943-946 943 the tissue content ofNP-SH and GSH. The data suggest that the effect of fasting is mediated through a change in the concentration of deiodinase rather than in the availability of cofactor.
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