Rapid Thyroxine to 3,5,3′-Triiodothyronine Conversion and Nuclear 3,5,3′-Triiodothyronine Binding in Rat Cerebral Cortex and Cerebellum

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Abstract
Thyroxine (T4) to 3,5,3′-triiodothyronine (T3) conversion was evaluated in vivo in cerebral cortex, cerebellum, and anterior pituitary of male euthyroid Sprague-Dawley rats. Tracer quantities of 125I-T4 and 131I-T3 were injected into controls and iopanoic acid-pretreated rats 3 h before isolation of nuclei from these tissues. Specifically-bound nuclear 131I-T3, denoted T3(T3); 125I-T3, denoted T3(T4); and 125I-T4 were extracted and identified by chromatography. Plasma iodothyronines were similarly quantitated. In control rats, nuclear T3(T3) (percent dose per milligram DNA × 10−4) was 174±31 in cerebral cortex, 50±9 in cerebellum, and 932±158 in pituitary (all values, mean±SEM). Nuclear T3(T4) (percent dose per milligram DNA × 10−4) was 23.3±3.3 in cortex, 3.5±0.6 in cerebellum, and 39.4±6.9 in pituitary. Two-thirds of nuclear T3(T4) derived from local T4 to T3 conversion. Nuclear T3(T4) in all tissues was reduced to less than 15% of its control value by iopanoic acid treatment and all of the residual nuclear T3(T4) could be accounted for by plasma T3(T4). Nuclear T3(T3) binding was not inhibited by iopanoic acid. These results indicate there is rapid local T4 to T3 conversion in rat brain and nuclear binding of the T3 produced. We have previously found that local T3(T4) production is the source of ∼50% of the T3 in rat anterior pituitary. The present observations that the ratio of locally derived nuclear T3(T4) to nuclear T3(T3) is much higher in cerebral cortex (0.1) and cerebellum (0.04) than in anterior pituitary (0.015) suggest that this locally produced T3(T4) is the predominant source of intracellular T3 in these portions of rat brain.

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