Regulation of the Conversion of Thyroxine to Triiodothyronine in the Perfused Rat Liver

Anthony S. Jennings; Duncan C. Ferguson; Robert D. Utiger

doi:10.1172/JCI109623

Regulation of the Conversion of Thyroxine to Triiodothyronine in the Perfused Rat Liver

Anthony S. Jennings, Duncan C. Ferguson, and Robert D. Utiger

Published December 1, 1979 - More info

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Abstract

This study was undertaken to determine what factors control the conversion of thyroxine (T₄) to triiodothyronine (T₃) in rat liver under conditions approximating those found in vivo. Conversion of T₄ to T₃ was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T₄ from perfusion medium and converted it to T₃. Production of T₃ by the perfused liver was a function of the size of the liver, the uptake of T₄ by the liver, and the presence of T₄-5′-deiodinase activity. Production of T₃ was increased by increasing the uptake of T₄ by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T₄ concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T₄ to T₃. The liver had a large capacity for extracting T₄ and for T₄-5′-deiodination to T₃, which was not saturated at a T₄ concentration of 60 μg/dl. Production of T₃ was decreased by inhibiting hepatic T₄-5′-deiodinase with propylthiouracil, which decreased T₃ production by decreasing the conversion of T₄ to T₃. Propylthiouracil did not alter hepatic T₄ uptake.

Fasting resulted in a progressive decrease in hepatic T₄ uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T₃ production. The rate of conversion of T₄ to T₃ did not change during fasting. When T₄ uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T₄ concentration from 10 to 30 μg/dl, T₃ production returned to normal. Again, no change in the rate of conversion of T₄ to T₃ was observed.

These results indicate that the decreased hepatic T₃ production during fasting primarily results from decreased hepatic uptake of T₄, rather than from changes in T₄-5′-deiodinase activity. Thus, these studies have delineated a new mechanism that functions independently of enzyme quantity or activity whereby production of T₃ from T₄ is regulated.