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It has been shown that the monodeiodination of T4 to either T3 or rT3 is an important step in T4 metabolism. Moreover, recent studies reported that T3 is converted further to either 3, 3'-T2 or 3, 5-T2 and rT3 is converted to either 3, 3'-T2 or 3', 5'-T2. To evaluate the physiological significance of the sequential monodeiodination of T4, several experiments were performed and the following results were obtained. (1) Serum 3,, 3', 5'-T2 and 3, 5-T2 as well as T4, T4 and rT3 concentrations were determined by RIAs in 81 normal subjects, aged 24-81 years. Although no significant relation existed between T4 levels and age, serum T3 showed a significant inverse correlation with age. In contrast, no significant correlation was observed between rT3 and age. Serum 3, 3-T2, 3', 5'-T2 and 3, 5-T2 values all had significant inverse correlation with age. These findings suggest that sequential monodeiodinating activities of T4 decrease with increasing age. (2) The conversion of T4 to T3 was studied in normal, Graves' and neoplastic thyroid tissues. The T3 generation in the thyroid tissue was dependent on the amount of tissue used, temperature and pH, suggesting the enzymatic nature of T4 5'-monodeiodinating activity in the thyroid. The conversion of T4 to T3 was observed in differentiated thyroid neoplasma and was markedly enhanced in Graves' thyroid tissues compared to that of normal thyroid tissues. (3) The conversion of T4 to T4 was studied in the rat anterior pituitary, using paper chromatography. The T3 generating activity from T4 increased with an increase in the amount of tissue and was temperature- and pH-dependent. T4 5'-monodeiodinating activity was consistently, though minimally, detected in fetal rat pituitaries and increased after birth, reaching the maximum at 22 days. Serum TSH levels were markedly elevated in the fetus. They decreased after birth, reaching their nadir at 22 days. Thus, a reciprocal relation was observed between intrapituitary T3 generating activity from T4 and serum TSH levels in developing rats. (4) The rT3 generation from T4 and 3, 3'-T2 generation from T3, representing T4 or T3 5-monodeiodination, and the conversion of rT3 to 3, 3'-T2, representing rT3 5'-monodeiodination, were studied in the p2 fraction of rat brain homogenate. T4 or T3 5-deiodinating activity was dependent upon the amount of the tissue, temperature and pH and was mainly found in synaptosomal fractions. Moreover, the conversion of rT3 to 3, 3'-T2 was also dependent on tissue amount, temperature and pH. T4 or T3 5-monodeiodinating activity was highest in the cerebral cortex and was far lower in the cerebellum, while rT3 5'-monodeiodinating activity was highest in the rat cerebellum and lower in the cerebral cortex. These findings suggest that two different deiodinases are present in the rat brain. (5) Studies were undertaken to define the existence of specific T3 binding sites in the synaptosomal fraction of the rat cerebral cortex. Scatchard analysis was compatible with the existence of two sets of high affinity T3 binding sites, the higher affinity, lower capacity site and the lower affinity, higher capacity site. In contrast to nuclear T3 receptors, the maximal binding capacity of the higher affinity synaptosomal T3 binding sites was low in neonatal rats and increased thereafter to the levels of adult rats, coinciding with the
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甲状腺ホルモン代謝並びに作用に関する最近の知見

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