COMPARISON OF THYROXINE AND 3,3',5'-TRIIODOTHYRONINE METABOLISM IN RAT-KIDNEY AND LIVER HOMOGENATES

The effects of agents added in vitro, in vivo PTU treatment, and fasting for 72 hr on T4-T3 conversion rates and rT3 degradation rates in rat kidney and liver homogenates were compared. In kidney homogenates, 5 mM DTT stimulated both reactions, whereas 0.3 mM diamide, 0.1 μM iopanoic acid, 17 μM PTU and 1 mM 2,4-dinitrophenol inhibited both reactions; 25 μM methimazole had no effect. DTT also stimulated both of these reactions in liver homogenates. Diamide was a less potent inhibitor in liver than in kidney homogenates. Kinetic analysis showed that the km for T4 in kidney and liver homogenates were similar, but not identical, and that the km for rT3 in kidney and liver homogenates were again similar, but not precisely the same. When a particulate fraction of the homogenates was employed, the km for T4 in two kidney preparations was 0.8 and 1.0 μM, and in two liver preparations it was 2.9 and 5.5 μM. PTU administered in vivo reduced the T4-T3 conversion rates and rT3 degradation rates in kidney and liver homogenates to < 20% of control, reduced the mean serum T3 concentration to < 33% of control, raised the mean serum rT3 concentration to nine times control, but did not alter the mean serum T4 concentration or the hepatic glutathione content. A 72-hr fast had no effect on T4-T3 conversion or rT3 degradation rates in kidney homogenates and had no effect on renal glutathione content, but fasting had the expected inhibitory effect on T4-T3 conversion in liver homogenates and lowered the hepatic glutathione content to 79% of control. These results, along with previous findings from this and other laboratories, strongly suggest that there is a single iodothyronine 5′-monodeio-dinase in rat kidney that metabolizes both T4 and rT3. The results are also compatible with the hypothesis that the iodothyronine 5′-monodeiodinases in rat kidney and liver are the same enzyme. © 1979.