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Modulating Effect of Glutathione Disulfide on Thyroxine-5'-Deiodination by Rat Hepatocytes in Primary Culture: Effect of Glucose^*

Department of Internal Medicine and Endocrinology, Tokyo Women’s Medical College Ichigaya-Kawadacho
The Foundation for Growth Science Shinjuku-ku, Tokyo, Japan

Address requests for reprints to: Dr. Kanji Sato, Department of Internal Medicine and Endocrinology, Tokyo Women's Medical College,Ichigaya-Kawadacho, Shinjuku-ku, Tokyo, Japan.

Abstract

To investigate whether an increase in the intracellular glutathione disulfide (GSSG) concentration actually regulates T₄-5'-deiodination in intact cells, rat hepatocytes in primary culture were exposed to glutathione-oxidizing agents (diamide and tertiary butylhydroperoxide) or vinblastine, and their effects on 5'-deiodination of T₄ were studied. Deiodinating activity was determined from the ¹²⁵I– fraction released from [3',5'-¹²⁵I]T₄ added to the serum-free culture medium. Total glutathione (T-GSH) and GSSG levels were determined enzymatically.

Diamide (1 mM) and tertiary butylhydroperoxide (0.5 mM) increased the GSSG fraction to approximately 40% of the TGSH at 5 min, followed by a rapid decrease in GSSG. Glucose deprivation of the medium caused a greater GSSG level at 5 min, followed by a delayed normalization of the increased GSSG level. T₄-5'-deiodinating activity was minimally decreased in hepatocytes exposed to 1 mM diamide in the presence of glucose in the medium, but was significantly inhibited in the absence of glucose. Vinblastine, in contrast, gradually and steadily increased the GSSG fraction, and by 3 h, GSSG exceeded 20% of T-GSH (at 10^–4 M vinblastine). This was accompanied by a significant inhibition of 5'-deiodinating activity. When the enzyme activity was inhibited, the T-GSH level was decreased to 40-80% of the control level, which per se cannot account for the decreased T₄-5'-deiodinating activity, as reported previously. These data suggest that the increased GSSG level, but not the T-GSH concentration, modulates T₄-5'-deiodination in intact cells, and that glucose stimulates the enzyme activity by maintaining glutathione in the reduced form, probably through supplying NADPH, a cofactor for GSSG reductase. (Endocrinology 113: 878,1983)

Footnotes

^* This work was supported by a research grant from the Foundation for Growth Science, Shinjuku-ku, Tokyo.

Received August 2, 1982.

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