Silva J E, Matthews P
Endocrinology. 1984 Jun;114(6):2394-405. doi: 10.1210/endo-114-6-2394.
Earlier studies have shown larger increments in serum T3 in 2-week-old congenitally hypothyroid rats than in euthyroid controls after injections of small doses of T4. Since hepatic and renal 5'-deiodination of T4 to T3 in vitro (5' D-I) is reduced during the neonatal period and in hypothyroidism, those results suggest that there may be major changes in the distribution and metabolism of T3 or that an alternative enzymatic pathway is the predominant source of extrathyroidally produced T3 in these rats. The alternative pathway, 5' D-II, is a relatively minor source of serum T3 in adult euthyroid rats, but the contribution of this pathway to the extrathyroid T3 pool during the neonatal period and in hypothyroxinemia is not known. Consequently, we studied [125I]T4 and [131I]T3 kinetics and fractional T4 to T3 conversion in 2-week-old euthyroid and hypothyroid rats and then explored the source of circulating T3 by manipulating 5' D-I activity with propylthiouracil and that of 5' D-II with thyroid hormone. The plasma clearance rate of T4 was increased in hypothyroid rats, a difference entirely accounted for by the faster fractional rate of irreversible removal in the hypothyroid pups. Plasma clearance rate of T3 was reduced in hypothyroid rats owing to the reduced volume of distribution of T3. Fractional T4 to T3 conversion was 2- to 3-fold higher in euthyroid or hypothyroid neonates than in adult rats. In euthyroid rats the serum concentration of T4 was 36 +/- 1 (SEM) ng/ml and that of T3 0.61 +/- 0.03 ng/ml, and the production rates were 432 and 159 ng day-1 30 g-1 BW for T4 and T3, respectively. About 80% of the T3 in euthyroid neonates was produced extrathyroidally . These findings are inconsistent with hepatic and renal 5' D-I being the main source of serum T3 in 2-week-old rats. In fact, liver and kidney 5' D-I activities were 40% and 65% of the corresponding adult values in euthyroid neonates, and in hypothyroid pups were further reduced to 15% and 17%. In contrast, 5' D-II, previously reported to be high in central nervous tissue and pituitary, was 7-10-fold higher in brown adipose tissue (BAT) of hypothyroid pups than in that of euthyroid ones.(ABSTRACT TRUNCATED AT 400 WORDS)
早期研究表明，给2周龄先天性甲状腺功能减退的大鼠注射小剂量T4后，其血清T3的升高幅度大于甲状腺功能正常的对照大鼠。由于新生儿期和甲状腺功能减退时，T4在肝脏和肾脏中体外5'-脱碘生成T3（5'D-I）的过程会减弱，这些结果表明，T3的分布和代谢可能发生了重大变化，或者在这些大鼠中，另一种酶促途径是甲状腺外产生T3的主要来源。替代途径5'D-II在成年甲状腺功能正常的大鼠中是血清T3的相对次要来源，但该途径在新生儿期和甲状腺素血症期间对甲状腺外T3池的贡献尚不清楚。因此，我们研究了2周龄甲状腺功能正常和甲状腺功能减退大鼠的[125I]T4和[131I]T3动力学以及T4到T3的分数转化率，然后通过用丙硫氧嘧啶调节5'D-I活性和用甲状腺激素调节5'D-II活性来探究循环T3的来源。甲状腺功能减退大鼠中T4的血浆清除率增加，这一差异完全是由甲状腺功能减退幼崽中更快的不可逆清除分数率所致。甲状腺功能减退大鼠中T3的血浆清除率降低，这是由于T3的分布容积减小。甲状腺功能正常或减退的新生儿中T4到T3的分数转化率比成年大鼠高2至3倍。在甲状腺功能正常的大鼠中，血清T4浓度为36±1（SEM）ng/ml，T3浓度为0.61±0.03 ng/ml，T4和T3的生成率分别为432和159 ng·天-1·30 g-1体重。甲状腺功能正常的新生儿中约80%的T3是甲状腺外产生的。这些发现与肝脏和肾脏5'D-I是2周龄大鼠血清T3的主要来源不一致。事实上，甲状腺功能正常的新生儿肝脏和肾脏的5'D-I活性分别为相应成年值的40%和65%，而在甲状腺功能减退的幼崽中进一步降至15%和17%。相比之下，先前报道在中枢神经组织和垂体中较高的5'D-II，在甲状腺功能减退幼崽的棕色脂肪组织（BAT）中比甲状腺功能正常的幼崽高7至10倍。（摘要截选至400字）
