Rapid Thyroxine to 353′-Triiodothyronine Conversion and Nuclear 353′-Triiodothyronine Binding in Rat Cerebral Cortex and Cerebellum

摘要

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.