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

甲状腺激素在大脑中代谢的研究因其极端的复杂性和异质性而受到阻碍。因此，我们试图建立更简单的系统来研究甲状腺激素在大脑中的代谢和作用。我们发现，在大鼠的后脑垂体腺和松果体中，存在着5-脱碘酶(5D-III)，它能特异性地灭活甲状腺激素，并在大脑中大量存在。脑垂体区的活动定位于神经叶，中间叶未见。这两个器官也有II型5‘-脱碘酶(5’D-II)，它能特异性地激活甲状腺激素。松果体5‘D-II也有明显的β-肾上腺素介导的夜间节律。同工酶在这些器官中的分布与在大脑中的分布非常相似。这些数据表明，甲状腺激素在这些器官中可能具有以前未被认识到的作用，这些可能是研究甲状腺激素在大脑中代谢的合适模型。大多数关于培养细胞中甲状腺激素代谢的研究都使用了神经胶质细胞，尽管最初的报道是5‘D-II定位于神经元。星形胶质细胞仅表达5D-III和5‘D-I，对甲状腺素的亲和力较低。5‘D-II只有在DBcAMP刺激后才能被诱导。我们利用培养的神经细胞，在稳定的条件下发现了5‘D-II和5D-III。因此，星形胶质细胞和神经元可能属于不同的代谢区段。脱碘酶的调节机制目前正在研究中。

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.