Evidence for a role of the type III-iodothyronine deiodinase in the regulation of 3,5,3 '-triiodothyronine content in the human central nervous system

Objective: Thyroid hormone is essential for maintaining normal neurological functions both during development and in adult life. Type III-iodothyronin e deiodinase (D3) degrades thyroid hormones by converting thyroxine and 3.5 ,3'-triiodothyroinine (T3) to inactive metabolites. A regional expression o f D3 activity has been observed in the human central nervous system (CNS), and a critical role for D3 has been suggested in the regulation of local T3 content in concert with other enzymes. Design: This study was undertaken to further characterize D3 activity in hu man CNS and to understand its role in the local regulation of T3 content. Methods: Autoptic specimens from various areas of human CNS were obtained 6 -27 h postmortem from 14 donors who died from cardiovascular accident, neop lastic disease or infectious disease. D3 was determined by measuring the co nversion of T3 to 3,3'-diiodothyronine. The T3 content was measured by radi oimmunoassay in ethanol extracts, using a specific antiserum. Results: High levels of D3 activity were observed in hippocampus and tempor al cortex, lower levels being found in the thalamus, hypothalamus, midbrain cerebellum, parietal and frontal cortex, and brain stem. An inverse relati onship between D3 activity and T3 content in these areas was demonstrated. Conclusions: We have concluded that D3 contributes to the local regulation of T3 content in the human CNS.