Rapid thyroxine to 3,5,3'-triiodothyronine conversion and nuclear 3,5,3'-triiodothyronine binding in rat cerebral cortex and cerebellum.
Thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) conversion was evaluated in vivo in cerebral cortex, cerebellum, and anterior pituitary of male euthyroid Sprague-Dawley rats. Tracer quantities of (125)I-T(4) and (131)I-T(3) were injected into controls and iopanoic acid-pretreated rats 3 h before isolation of nuclei from these tissues. Specifically-bound nuclear (131)I-T(3), denoted T(3)(T(3)); (125)I-T(3), denoted T(3)(T(4)); and (125)I-T(4) were extracted and identified by chromatography. Plasma iodothyronines were similarly quantitated. In control rats, nuclear T(3)(T(3)) (percent dose per milligram DNA x 10(-4)) was 174+/-31 in cerebral cortex, 50+/-9 in cerebellum, and 932+/-158 in pituitary (all values, mean+/-SEM). Nuclear T(3)(T(4)) (percent dose per milligram DNA x 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 T(3)(T(4)) derived from local T(4) to T(3) conversion. Nuclear T(3)(T(4)) in all tissues was reduced to less than 15% of its control value by iopanoic acid treatment and all of the residual nuclear T(3)(T(4)) could be accounted for by plasma T(3)(T(4)). Nuclear T(3)(T(3)) binding was not inhibited by iopanoic acid. These results indicate there is rapid local T(4) to T(3) conversion in rat brain and nuclear binding of the T(3) produced. We have previously found that local T(3)(T(4)) production is the source of approximately 50% of the T(3) in rat anterior pituitary. The present observations that the ratio of locally derived nuclear T(3)(T(4)) to nuclear T(3)(T(3)) is much higher in cerebral cortex (0.1) and cerebellum (0.04) than in anterior pituitary (0.015) suggest that this locally produced T(3)(T(4)) is the predominant source of intracellular T(3) in these portions of rat brain.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D007480:Iopanoic Acid / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis*
D014284:Triiodothyronine; D007480:Iopanoic Acid; D013974:Thyroxine