Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid.
The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation.
Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid. The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation.