Regional expression of the type 3 iodothyronine deiodinase messenger ribonucleic acid in the rat central nervous system and its regulation by thyroidhormone

Type 3 iodothyronine deiodinase (D3) is a selenoenzyme that inactivates thy roid hormone. It is necessary for T-3 homeostasis in the central nervous sy stem. D3 activity has been identified in many regions of the brain and para llels thyroid status, but the level at which it is regulated and its specif ic cellular locations are not known. We evaluated the effect of thyroid sta tus on the expression of the D3 gene within the central nervous system usin g in situ hybridization histochemistry. D3 messenger RNA (mRNA) was identif ied throughout, but with high focal expression in the hippocampal pyramidal neurons, granule cells of the dentate nucleus, and layers II-VI of the cer ebral cortex. In every region, D3 mRNA abundance was correlated with thyroi d status. Four different D3 transcripts were identified by Northern analyse s, with evidence for region-specific processing, and D3 mRNA increased 4- t o 50-fold from the euthyroid to the hyperthyroid state. D3 mRNA was not det ectable in hypothyroid brain. In the central nervous system, the D3 gene is highly T-3 responsive. and its focal localization within the hippocampus a nd cerebral cortex suggests an important role for T-3 homeostasis in memory and cognitive functions.