Comparison of thyroxine and 3,3′,5′-triiodothyronine metabolism in rat kidney and liver homogenates

Abstract

The effects of agents added in vitro, in vivo PTU treatment, and fasting for 72 hr on T 4-T 3 conversion rates and rT 3 degradation rates in rat kidney and liver homogenates were compared. In kidney homogenates, 5 m M DTT stimulated both reactions, whereas 0.3 m M diamide, 0.1 μ M iopanoic acid, 17 μ M PTU and 1 m M 2,4-dinitrophenol inhibited both reactions; 25 μ M 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 k m for T 4 in kidney and liver homogenates were similar, but not identical, and that the k m for rT 3 in kidney and liver homogenates were again similar, but not precisely the same. When a particulate fraction of the homogenates was employed, the k m for T 4 in two kidney preparations was 0.8 and 1.0 μ M, and in two liver preparations it was 2.9 and 5.5 μ M. PTU administered in vivo reduced the T 4-T 3 conversion rates and rT 3 degradation rates in kidney and liver homogenates to < 20% of control, reduced the mean serum T 3 concentration to < 33% of control, raised the mean serum rT 3 concentration to nine times control, but did not alter the mean serum T 4 concentration or the hepatic glutathione content. A 72-hr fast had no effect on T 4-T 3 conversion or rT 3 degradation rates in kidney homogenates and had no effect on renal glutathione content, but fasting had the expected inhibitory effect on T 4-T 3 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 T 4 and rT 3. The results are also compatible with the hypothesis that the iodothyronine 5′-monodeiodinases in rat kidney and liver are the same enzyme.