Studies on the metabolism and action of thyroid hormone with emphasis on its role in neurotransmission

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Studies of the thyroid hormone metabolism in the brain have been hampered by its extreme complexity and heterogenity. Thus we tried to establish more simplified systems to study the metabolism and action of thyroid hormone in the brain.We found that type-III 5-deiodinase (5D-III), which specifically inactivates thyroxine and is abundant in the brain, in rat posterior pituitary and pineal gland. The activity in the pituitary was localized in the neural lobe and was not found in the intermediate lobe. These two organs also have type-II 5'-deiodinase (5'D-II), which specifically activates thyroxine. Pineal 5'D-II also has a marked beta-adrenergically mediated nyctohemeral rhythm. Isozyme distribution in these organs are quite similar to that in the brain. These data suggest that thyroid hormone is likely to have previously unrecognized role in these organs and these can be suitable models to study thyroid hormone metabolism in the brain.Most studies on thyroid hormone metabolism in cultured cells have employed glial cells, although 5'D-II were initially reported to be localized in neurons. Astrocytes exibit only 5D-III and 5'D- I, which has low affinity for thyroxine. 5'D-II is induced only after stimulation by dbcAMP. We used cultured neuronal cells and found 5'D-II and 5D-III under steady condition. Thus astrocytes and neurons are likely to belong to different metabolic compartment.Regulatory mechanism of deiodinases are now under study.