POTENTIAL OF BROWN ADIPOSE-TISSUE TYPE-II THYROXINE 5'-DEIODINASE AS A LOCAL AND SYSTEMIC SOURCE OF TRIIODOTHYRONINE IN RATS
POTENTIAL OF BROWN ADIPOSE-TISSUE TYPE-II THYROXINE 5'-DEIODINASE AS A LOCAL AND SYSTEMIC SOURCE OF TRIIODOTHYRONINE IN RATS
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DOI：
10.1172/jci112239
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发表时间：
1985-12-01
影响因子：
15.9
通讯作者：
LARSEN, PR
中科院分区：
文献类型：
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作者：
SILVA, JE;LARSEN, PR
先前的报告表明，当酶水平充分升高和/或肝脏和肾脏 I 型 5''-脱碘酶活性降低时，II 型碘甲状腺原氨酸 5''-脱碘酶可能成为甲状腺外三碘甲状腺原氨酸（T3）生成的主要酶促途径。目前的研究评估了棕色脂肪组织 (BAT) II 型 5''-脱碘酶为血浆库生成 T3 的潜力。通过短期（4小时）或长期（7周）冷暴露（4°C）刺激BAT 5''-脱碘（BAT 5''D）。长期寒冷暴露会使甲状腺素 (T4) 分泌增加 40-60%，甲状腺外 T3 产量增加三倍。在接受丙硫氧嘧啶 (PTU) 治疗的冷适应大鼠中，甲状腺外 T3 的产生量比维持在室温下的 PTU 治疗的大鼠高 10 倍。寒冷不会刺激肝脏或肾脏 5''D，但适应寒冷的大鼠的 BAT 5''D 含量要高出六到八倍。 PTU 对肝脏和肾脏 5''D 造成 > 95% 的抑制，但不影响 BAT 5''D。每天维持0.8μg T4/100g体重(BW)的甲状腺切除大鼠急性暴露于4°C。 C. 在给予 10 mg PTU/100 g BW 的大鼠中，4 小时的冷暴露仍然导致 BAT 5''D 增加 12 倍，血浆 T3 产量增加 2.3 倍，BAT 本身局部产生的 T3 增加 4.8 倍。所有这些反应均通过用α1-抗肾上腺素药物哌唑嗪预处理而消除。无论环境温度如何，肝脏 5''D 活性均被 PTU 抑制 > 90%。这些结果表明，在适当的情况下，例如急性或慢性暴露于寒冷下，BAT可以成为血浆T3的主要来源。此外，BAT 5''D 活性影响 BAT T3 含量本身，这表明甲状腺激素在增强该组织对交感神经刺激的生热反应方面可能具有以前未被认识到的作用。这种相互作用在人类新生儿早期（生热应激明显的时期）可能尤其重要。
Previous reports suggest that a type II iodothyronine 5''-deiodinase may become the main enzymatic pathway for extrathyroidal triiodothyronine (T3) generation when the enzyme levels are sufficiently elevated and/or liver and kidney type I 5''-deiodinase activity is depressed. The present studies assessed the potential of brown adipose tissue (BAT) type II 5''-deiodinase to generate T3 for the plasma pool. BAT 5''-deiodination (BAT 5''D) was stimulated by either short- (4 h) or long-term (7 wk) cold exposure (4.degree. C). Long-term cold exposure increased thyroxine (T4) secretion 40-60% and extrathyroidal T3 production three-fold. In cold-adapted rats treated with propylthiouracil (PTU), extrathyroidal T3 production was 10-fold higher than in PTU-treated rats maintained at room temperature. Cold did not stimulate liver or kidney 5''D, but the cold-adapted rats showed a six-to eightfold higher BAT 5''D content. PTU caused > 95% inhibition of liver and kidney 5''D, but did not affect BAT 5''D. Thyroidectomized rats maintained on 0.8 .mu.g of T4/100 g of body weight (BW) per day were acutely exposed to 4.degree. C. In rats given 10 mg of PTU/100 g of BW, 4 h of cold exposure still caused a 12-fold increase in BAT 5''D, a 2.3-fold increase in plasma T3 production, and a 4.8-fold increment in the locally produced T3 in BAT itself. All these responses were abolished by pretreatment with the .alpha.1-antiadrenergic drug prazosin. Regardless of the ambient temperature, liver 5''D activity was > 90% inhibited by PTU. These results indicate that BAT can be a major source of plasma T3 under suitable circumstances such as acute or chronic exposure to cold. Furthermore, BAT 5''D activity affects BAT T3 content itself, suggesting that thyroid hormone may have a previously unrecognized role in augmenting the thermogenic response of this tissue to sympathetic stimulation. Such interactions may be especially important during the early neonatal period in humans, a time of marked thermogenic stress.