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. 1978 Feb;61(2):459–471. doi: 10.1172/JCI108957

Iodothyronine Metabolism in Rat Liver Homogenates

Michael M Kaplan 1, Robert D Utiger 1
PMCID: PMC372557  PMID: 340472

Abstract

To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and degradation of 3,3′,5′-triiodothyronine (rT3) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T4 to T3, the Km of T4 was 7.7 μM, and the Vmax was 0.13 pmol T3/min per mg protein. For rT3 degradation, the Km of rT3 was 7.5 nM, and the Vmax was 0.36 pmol rT3/min per mg protein. Production of rT3 or degradation of T4 or T3 was not detected under the conditions employed. rT3 was a potent competitive inhibitor of T4 to T3 conversion with a Ki of 4.5 nM; 3,3′-diiodothyronine was a less potent inhibitor of this reaction. T4 was a competitive inhibitor of rT3 degradation with a Ki of 10.2 μM. Agents which inhibited both reactions included propylthiouracil, which appeared to be an allosteric inhibitor, 2,4-dinitrophenol, and iopanoic acid. Sodium diatrizoate had a weak inhibitory effect. No inhibition was found with α-methylparatyrosine, Fe+2, Fe+3, reduced glutathione, β-hydroxybutyrate, or oleic acid.

Fasting resulted in inhibition of T4 to T3 conversion and of rT3 degradation by rat liver homogenates which was reversible after refeeding. Serum T4, T3, and thyrotropin concentrations fell during fasting, with no decrease in serum protein binding as assessed by a T3-charcoal uptake. There was no consistent change in serum rT3 concentrations. Dexamethasone had no effect in vitro. In vivo dexamethasone administration resulted in elevated serum rT3 concentrations after 1 day, and after 5 days, in inhibition of T4 to T3 conversion and rT3 degradation without altering serum T4, T3, or thyrotropin concentrations. Endotoxin treatment had no effect of iodothyronine metabolism in liver homogenates. In kidney homogenates the reaction rates and response to propylthiouracil in vitro were similar to those in liver. No significant T4 to T3 conversion or rT3 production or degradation could be detected in other tissues.

These data suggest that one iodothyronine 5′-deiodinase is responsible for both T4 to T3 conversion and rT3 degradation in liver and, perhaps, in kidney. Alterations in serum T3 and rT3 concentrations induced by drugs and disease states may result from decreases in both T3 production and rT3 degradation consequent to inhibition of a single reaction in the pathways of iodothyronine metabolism.

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Selected References

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