Changes in hepatic iodothyronine metabolism during ontogeny of the chick embryo.
Changes in hepatic iodothyronine metabolism during ontogeny of the chick embryo.
复制标题
鸡胚个体发育过程中肝脏碘甲状腺氨酸代谢的变化。
DOI：
10.1210/endo-107-6-1751
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发表时间：
1980
期刊：
影响因子：
4.8
通讯作者：
S. Ingbar
中科院分区：
文献类型：
--
作者：
M. Borges;J. LaBourene;S. Ingbar
作为个体发育过程中外周碘甲状腺原氨酸代谢变化的模型，我们研究了~(125)I标记的T4及其几个部分去碘的衍生物在鸡胚胎肝脏中的代谢。将8天至孵化(20-21天)不同胎龄雏鸡的肝脏匀浆与各种碘甲状腺原氨酸孵育，均在其外环或酚环标记~(125)I。用全匀浆纸层析法对反应速率和产物进行分析。在所有研究年龄段的胚胎肝脏中，添加二硫苏糖醇(DTT；2 mM)可提高碘甲状腺原氨酸T4、T3和RT3的代谢率。碘甲状腺原氨酸代谢的显著年龄相关变化是明显的；在没有DTT的情况下，这些变化很明显，但在添加了DTT的标本中最明显。RT3的降解非常迅速，甚至在8日龄胚胎的肝脏中也是如此，但其降解速度随着胚胎年龄的增加而递增，直到孵化。外环(5‘-)单脱碘生成3，3’-二碘甲腺原氨酸(3，3‘-T2)，是整个胚胎发育过程中RT3代谢的主要途径，也可能是唯一途径。T4和T3代谢的年龄相关变化彼此相似，但与RT3的情况有很大不同。在富含DTT的样品中，T4和T3在12日龄胚胎肝脏中的代谢速度较快，然后急剧增加，在胚胎肝脏中保持非常快的代谢速度，直到18日龄。T4的快速降解不是由于5‘-单脱碘，因为T4产生的T3很少。此外，由于在空气和氮气中孵育的结果相似，T4的氧化降解显然并不重要。相反，在此期间，内环(5-)单脱碘似乎是T4和T3代谢的主要途径，导致T4形成RT3，T3形成3，3‘-T2。在19日龄和20日龄胚胎的肝脏中，后者在孵化前获得，由于5-单脱碘速率的降低，T4和T3的整体代谢突然和逐渐减慢。同时，T3和T4的5‘-单脱碘作用变得更加突出，导致从T4产生更多的T3。T4和T3代谢的这些成熟变化在时间上与胚胎喙进入气囊并启动空气呼吸的过程相一致，这一过程被称为内吸管。在未成熟胚胎的尿囊膜上一次性注射200微克氢化可的松，可在2天内引起T4和T3代谢的早熟变化，这与19日龄胚胎特别是20日龄胚胎自发发生的变化非常相似。结论：肝脏碘甲状腺原氨酸在未成熟胚胎中的代谢是定向的，以防止T_4来源的T_3蓄积。
As a model of the changes in peripheral iodothyronine metabolism that occur during ontogeny, we have studied the metabolism of 125I-labeled T4 and several of its partially deiodinated derivatives by the liver of the chick embryo. Homogenates of livers obtained from chicks varying in embryonic age from 8 days to the time of hatching (20-21 days) were incubated with various iodothyronines, all labeled with 125I in their outer or phenolic ring. Rates and products of the reactions were analyzed by paper chromatography of whole homogenates. In livers from embryos of all ages studied, the addition of dithiothreitol (DTT; 2 mM) enhanced the rate of metabolism of the iodothyronines T4, T3, and rT3. Marked age-related changes in the metabolism of the iodothyronines were apparent; these were evident in the absence of DTT, but were most clearly seen in specimens to which DTT had been added. rT3 was degraded very rapidly, even in livers from 8-day-old embryos, but its rate of degradation increased progressively with increasing age of the embryo up to the time of hatching. Outer ring (5'-) monodeiodination, giving rise to 3,3'-diiodothyronine (3,3'-T2), was the predominant, and perhaps the sole, pathway of rT3 metabolism throughout this period of embryogenesis. Age-related changes in the metabolism of T4 and T3 were similar to one another, but differed greatly from those seen in the case of rT3. In specimens enriched with DTT, the rates of metabolism of T4 and T3 were moderately rapid in livers from 12-day-old embryos and then increased abruptly, remaining very rapid in livers from embryos through 18 days of age. Rapid degradation of T4 was not due to 5'-monodeiodination, since very little T3 was generated from T4. In addition, since results obtained were similar during incubations under air and N2, oxidative degradation of T4 was apparently not important. Rather, during this period, inner ring (5-) monodeiodination appeared to be by far the predominmant pathway of metabolism of both T4 and T3, leading to the formation of rT3 from T4 and 3,3'-T2 from T3. In livers from 19- and 20 day-old embryos, the latter obtained just before hatching, the overall metabolism of both T4 and T3 slowed abruptly and progressively owing to a decrease in the rate of 5-monodeiodination. Concomitantly, 5'-monodeiodination of T3 and T4 became more prominent, leading to increased generation of T3 from T4. These maturational changes in T4 and T3 metabolism coincided in time with penetration of the air sac by the embryo's beak and initiation of air breathing, a process termed internal pipping. Premature maturational changes in T4 and T3 metabolism, very similar to those that occurred spontaneously in 19- and especially 20-day-old embryos, were induced within 2 days by the single injection of 200 microgram hydrocortisone onto the allantoic membrane of immature embryos. It is concluded that hepatic iodothyronine metabolism in the immature embryo is directed so as to prevent the accumulation of T3 derived from T4...