In vivo saturation studies of thyroidectomized, propylthiouracil, and L-triiodothyronine treated animals indicate that the hepatic nuclear binding capacity is not significantly influenced by the thyroidal status of the tissues. The constancy of the nuclear binding capacity for L-triiodothyronine facilitated an analysis of the relationship between nuclear occupancy and hepatic response to an intravenous injection of a triiodothyronine pulse. The activity of the mitochondrial enzyme alpha-glycerophosphate dehydrogenase was used as an index of tissue response to the administered triiodothyronine. Results were compatible with the following model. Saturation of nuclear sites is rapidly followed by a maximal rate of enzyme synthesis. When the sites are saturated, the activity of alpha-glycerophosphate dehydrogenase appeared to be independent of the dose administered. Higher doses of triiodothyronine achieve greater effects simply by occupying nuclear sites for a longer period. The apparent ability of nuclear sites to constrain tissue response to hormone administration provides additional supporting data for the physiological relevance of these sites in the initiation of hormonal action.
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