Alterations in hepatic monodeiodination of iodothyronines in the diabetic rat.
Alterations in hepatic monodeiodination of iodothyronines in the diabetic rat.
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糖尿病大鼠肝脏碘化甲状腺原氨酸单脱碘的变化。
DOI：
10.1016/0024-3205(81)90348-9
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发表时间：
1981
期刊：
影响因子：
6.1
通讯作者：
Frank,H
中科院分区：
文献类型：
--
作者：
Chopra,IJ;Wiersinga,W;Frank,H
第1天，大鼠静脉注射链脲佐菌素（65 mg/kg体重）或对照物，第7天检测甲状腺功能和肝脏匀浆对碘甲状腺原氨酸的单去碘作用。链脲佐菌素处理的动物血清葡萄糖浓度显著升高（平均±SEM， 476±21比144±5.6,mg/dl, p <0.001）。链脲佐菌素治疗的糖尿病大鼠血清游离t3的平均浓度明显低于对照组，糖尿病大鼠血清游离t4和TSH的平均浓度与对照组的相应值无显著差异。糖尿病大鼠肝匀浆对t4的外环单脱碘作用明显低于对照组。这是在存在和不存在4 nM二硫苏糖醇（DTT）的情况下的情况，DTT是硫醇（SH）基团的有效供体。在糖尿病大鼠和对照大鼠的肝脏中发现了相似浓度的非蛋白SH组，这也表明可用SH组的减少并不是导致糖尿病患者肝脏t4到t3转化活性降低的主要因素。这些发现表明，肝脏t4到t3转化活性的降低可能是由于T45 ' -单脱碘酶的减少。与t4到T3的转化一样，糖尿病大鼠肝脏外环逆T3(rT3)（转化为3,3 ' -二碘甲状腺原氨酸，3,3 ' -T2）和3 ',5 ' -T2（转化为3 ' -单碘甲状腺原氨酸，3 ' -1）的单去碘化也降低。这些数据支持了先前的发现，即只有一种外环单脱碘酶作用于各种碘甲状腺原氨酸。肝内环单去碘化T3（至3,3′-T2）和3,5-T2（至3- t1）也有所减少。在实验过程中，我们还比较了对照组和糖尿病大鼠肝脏匀浆中不同的单去碘作用。t4治疗的糖尿病大鼠肝脏匀浆的各种单去碘没有减少或只有适度减少（统计学上不显著）。与未接受外源性t4的糖尿病动物相比，接受外源性t4的糖尿病动物血清t4显著升高，血清t3中度升高。同样，给予T4的糖尿病大鼠肝脏中各种碘甲状腺原氨酸的单去碘化程度普遍高于未给予T4的大鼠。这些发现表明，循环甲状腺激素的减少，如前所述，可能在维持糖尿病患者肝脏碘甲状腺原氨酸单去碘化的减少中起重要作用。现在很清楚，甲状腺素（T4）的甲状腺外单去碘是人类和实验动物中3,5,3 ' -三碘甲状腺原氨酸（T3）的主要来源（1-7）。在许多临床情况下，甲状腺外的t3来源对每日总t3产生的贡献明显减少(7)。这些情况通常被称为低T3综合征，其特征是血清T3浓度低于正常，同时血清t4正常或低，逆转录T3（rT3）浓度正常（5,7）。当研究实验动物组织中t4到t3转化活性的性质时，数据表明活性本质上是酶性的（8,9），硫醇（SH）基团构成了活性的重要辅助因子（10,11），活性主要位于肝脏和肾脏匀浆的微粒体和/或质膜部分（12-14）。其他对不同实验物种胎儿（11,15 - 17）和禁食大鼠（9,17 - 19）的研究表明，可能有不止一种机制降低肝脏t4到T3的转化。例如，它……
Streptozotocin (65 mg/kg body weight) or vehicle was administered intravenously to rats on day 1 and thyroid function and monodeiodination of iodothyronines by liver homogenates were examined on day 7. Serum glucose concentration was markedly elevated in streptozotocin-treated animals (mean ± SEM, 476 ± 21 vs. 144 ± 5.6, mg/dl, p <0.001). The mean serum concentration of free T3in streptozotocin-treated diabetic animals was significantly less than that in vehicle-injected control rats, the mean serum concentration of free T4and TSH in diabetic rats did not differ significantly from the corresponding values in control rats. Outer ring monodeiodination of T4by liver homogenates was much lower in diabetic rats than in control rats. This was the case in the presence as well as in the absence of 4 nM dithiothreitol (DTT), a potent doner of thiol (SH) groups. That a reduction in available SH groups is not a major factor responsible for reduced hepatic T4to T3converting activity in diabetes mellitus was also suggested by the finding of a similar concentration of nonprotein SH groups in the liver of diabetic and control rats. These findings suggest that observed reduction in hepatic T4to T3converting activity is probably due to a reduction in the T45′-monodeiodinase. Like T4to T3conversion, hepatic outer ring monodeiodination of reverse T3(rT3) (to 3,3′-diiodothyronine, 3,3′-T2) and 3′,5′-T2(to 3′-monoiodothyronine, 3′-1) were also reduced in the diabetic rat. These data support previous findings suggesting that there is just one outer ring monodeiodinase that acts on various iodothyronines. There was also a reduction in hepatic inner ring monodeiodination of T3(to 3,3′-T2) and 3,5-T2(to 3-T1). The various monodeiodinations were also compared in liver homogenates of control and diabetic rats given exogenous T4(1 μg/100 g.b.w./day) throughout the experiment. There was no reduction or only a modest reduction (that was not significant statistically) in the various monodeiodinations by liver homogenates of T4treated diabetic rats. Serum T4was significantly higher and serum T3moderately higher in diabetic animals that received exogenous T4than in those that did not. Similarly, hepatic monodeiodination of various iodothyronines was generally greater in diabetic rats given T4than in those not given T4. These findings suggest that the reduction in the circulating thyroid hormones, described already, may have an important role in sustaining the reduction in hepatic monodeiodination of iodothyronines in diabetes mellitus.It is clear now that extrathyroidal monodeiodination of thyroxine (T4) is the major source of 3,5,3′-triiodothyronine (T3) in man and experimental animals (1–7). There are a number of clinical conditions in which the contribution of the extrathyroidal source of T3to the total daily production of T3is markedly reduced (7). These situations, which are often referred to as the low T3syndrome, are characterized by a subnormal serum T3concentration in combination with a normal or low serum T4and a normal of high reverse T3(rT3) concentrations (5,7). When the nature of T4to T3converting activity in tissues of experimental animals is examined, the data suggest that the activity is enzymic in nature (8,9), that thiol (SH) groups constitute a vital cofactor for the activity (10,11), and that the activity is located predominantly in microsomal and/or plasma membrane fractions of liver and kidney homogenates (12–14). Other studies in fetuses of various experimental species (11,15–17) and in the fasted rat (9,17–19) have revealed that there may be more than one mechanism of reduced hepatic conversion of T4to T3. For example, it …
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培养猴肝癌细胞中的甲状腺激素代谢。
影响因子：
4.8
作者：
K. Sato;J. Robbins
通讯作者：
J. Robbins
大鼠肝脏中甲状腺素脱碘的饮食调整不是由肝巯基介导的。
DOI：
10.1172/jci109751
发表时间：
1980
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
L. Gavin;F. McMAHON;M. Moeller
通讯作者：
M. Moeller
巯基和甲状腺素单脱碘为三碘甲状腺原氨酸。
影响因子：
56.9
作者：
I. Chopra
通讯作者：
I. Chopra
巯基对甲状腺功能减退、饥饿、胎儿和新生啮齿动物肝脏从甲状腺素生成 3,3,5-三碘甲状腺原氨酸受损的作用。
DOI：
10.1172/jci109330
发表时间：
1979
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
A. Harris;S. Fang;L. Hinerfeld;L. Braverman;A. Vagenakis
通讯作者：
A. Vagenakis
血清中三碘甲状腺原氨酸的改进放射免疫测定法：其在临床和生理研究中的应用。
DOI：
--
发表时间：
1972
期刊：
Journal of Laboratory and Clinical Medicine
影响因子：
--
作者：
Inder J. Chopra;Ruey S. Ho;Robert W. Lam
通讯作者：
Robert W. Lam