The role of sulfhydryl groups on the impaired hepatic 3',3,5-triiodothyronine generation from thyroxine in the hypothyroid, starved, fetal, and neonatal rodent.
The role of sulfhydryl groups on the impaired hepatic 3',3,5-triiodothyronine generation from thyroxine in the hypothyroid, starved, fetal, and neonatal rodent.
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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
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
A. Vagenakis
中科院分区：
文献类型：
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作者：
A. Harris;S. Fang;L. Hinerfeld;L. Braverman;A. Vagenakis
本文研究了非蛋白巯基（NPSH）在饥饿、甲状腺功能减退、胎儿和1 ~ 4d龄新生大鼠和侏儒小鼠体外肝脏甲状腺素（T（4））生成3 '，3，5-三碘甲状腺原氨酸（T（3））减少中的作用。在0.1 M PO（4）/10 mM EDTA缓冲液中制备的新鲜25%肝匀浆中测量NPSH。与成年雄性大鼠相比，饥饿2天后，（1.1 ± 0.04（平均值± SE）vs. 2.2 ± 0.15 mmol/250 g湿肝重，P < 0.001），胎儿（1.0+/-0.04 vs. 3.2+/-0.08，P < 0.001）、1日龄新生大鼠（1.1+/-0.03 vs. 2.1+/-0.04，P < 0.001）和甲状腺功能减退（甲状腺切除60天）大鼠（1.4+/-0.06 vs. 2.2+/-0.15，P < 0.001）。与正常同窝小鼠相比，甲状腺功能减退、低血压侏儒小鼠的NPSH也降低（1.3 ± 0.03 vs. 2.0 ± 0.2，P < 0.01）。长期给予T（3）（0.5 μ g/100 g体重/d）可显著增加甲状腺切除大鼠和侏儒小鼠肝脏T（3）的生成，使其值与正常啮齿动物中观察到的值相似，但不影响NPSH浓度。与此相反，饥饿大鼠给予T（3）并不改变T（4）或NPSH的肝脏T（3）生成。在饥饿大鼠中还原型谷胱甘肽浓度也显著降低（进食; 1.05+/-0.075 mmol/250 g湿组织vs.饥饿0.38+/-0.02，P < 0.001）。二硫苏糖醇（DTT）是一种巯基还原剂，在6项实验中，使正常成年雄性大鼠肝脏中T（4）生成T（3）的量增加了45+/-5%。与DTT刺激的对照匀浆相比，添加DTT完全恢复了饥饿大鼠肝脏T（3）的产生，部分恢复了1天和4天龄新生儿的T（3）产生，但对胎儿和甲状腺功能减退大鼠和侏儒小鼠几乎没有影响。在-20 ℃下储存6个月的肝匀浆失去了从T（4）生成T（3）的能力。冷冻匀浆中的NPSH浓度随着储存时间的增加而逐渐降低，6个月时不存在。5 ′-脱碘酶活性与NPSH浓度呈显著正相关（r = 0.95，P < 0.005）。DTT的加入部分恢复了冷冻匀浆中肝T（3）的产生。因此，NPSH对肝脏5 ′-脱碘酶的作用是重要的。饥饿大鼠肝脏T（3）生成的减少与NPSH的减少有关，但与5 ′-脱碘酶绝对量的减少无关，因为巯基的提供使肝脏T（3）生成恢复正常。相反，甲状腺功能减退的成年啮齿类动物和胎鼠的肝脏T（3）生成减少可能是由于酶浓度本身的降低。在1天和4天的新生大鼠中，肝脏T（3）生成的减少继发于NPSH和脱碘酶的减少。
The role of nonprotein sulfhydryl groups (NPSH) in the decreased in vitro hepatic 3',3,5-triiodothyronine (T(3)) generation from thyroxine (T(4)) in the starved, hypothyroid, fetal and 1- to 4-d-old neonatal rat and dwarf mouse was assessed. NPSH were measured in fresh 25% liver homogenates prepared in 0.1 M PO(4)/10 mM EDTA buffer. As compared with values in adult male rats, NPSH concentration was decreased in the 2-d-starved (1.1+/-0.04 (mean+/-SE) vs. 2.2+/-0.15 mmol/250 g wet liver weight, P < 0.001), fetal (1.0+/-0.04 vs. 3.2+/-0.08, P < 0.001), 1-d-old neonatal (1.1+/-0.03 vs. 2.1+/-0.04, P < 0.001), and hypothyroid (thyroidectomized 60 d) (1.4+/-0.06 vs. 2.2+/-0.15 P < 0.001) rat. NPSH were also decreased in the hypothyroid, hypopituitary dwarf mouse as compared with values in their normal litter mates (1.3+/-0.03 vs. 2.0+/-0.2, P < 0.01). Chronic administration of T(3) (0.5 mug/100 g body wt per d) markedly increased hepatic T(3) generation from T(4) in the thyroidectomized rat and in the dwarf mouse to values similar to those observed in the normal rodent without affecting NPSH concentration. In contrast, T(3) administration to the starved rat did not alter either hepatic T(3) generation from T(4) or NPSH. Reduced glutathione concentration was also markedly decreased in the starved rat (fed; 1.05+/-0.075 mmol/250 g wet tissue vs. starved 0.38+/-0.02, P < 0.001). Dithiothreitol (DTT), a thiol reducing agent, increased hepatic T(3) generation from T(4) in the normal adult male rat by 45+/-5% in six experiments. When compared to DTT-stimulated control homogenates, the addition of DTT completely restored hepatic T(3) generation in starved rats, partially restored T(3) generation in 1- and 4-d-old neonates, but had little or no effect in the fetal and hypothyroid rat and dwarf mouse. Liver homogenates stored for 6 mo at -20 degrees C lost their capacity to generate T(3) from T(4). NPSH concentrations in the frozen homogenates decreased progressively with increasing storage and were absent by 6 mo. 5'-Deiodinase activity correlated with NPSH concentration in the stored homogenates (r = 0.95, P < 0.005). Addition of DTT partially restored hepatic T(3) generation in the frozen homogenate. It is concluded that NPSH are important for the action of the liver 5'-deiodinase. The decreased hepatic T(3) generation in the starved rat is associated with decreased NPSH but not with a decrease in the absolute quantity of 5'-deiodinase because provision of sulfhydryl groups restored hepatic T(3) generation to normal. In contrast, the decreased hepatic T(3) generation in the adult hypothyroid rodent and in the fetal rat is probably due to a decrease in the enzyme concentration per se. In the 1- and 4-d neonatal rat, the decrease in hepatic T(3) generation is secondary to a decrease in NPSH and the deiodinating enzyme.