Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal [corrected] Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice.

Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal [corrected] Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice.
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DOI:
10.3389/fphys.2017.00828
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发表时间:
2017
影响因子:
4
通讯作者:
Ortiga-Carvalho TM
Ortiga-Carvalho TM
中科院分区:
医学2区
文献类型:
--
作者:
Fontes KN;Cabanelas A;Bloise FF;de Andrade CBV;Souza LL;Wilieman M;Trevenzoli IH;Agra LC;Silva JD;Bandeira-Melo C;Silva PL;Rocco PRM;Ortiga-Carvalho TM

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空腹和脓毒症引起甲状腺激素(TH)中枢和外周代谢的深刻变化。这些变化影响TH的作用,被称为非甲状腺疾病综合征(NTIS)。迄今为止,它仍然是有争议的,是否NTIS代表一种适应性反应或真实的甲状腺功能减退状态在组织水平。此外,即使它被认为是同一种综合征,我们假设禁食和脓毒症引起甲状腺激素代谢的一组不同的变化。在此,我们的目的是评估中枢和外周表达的基因参与运输(MCT 8/Slc 16 a2和MCT 10/Slc 16 a10),代谢(Dio 1,Dio 2和Dio 3)和行动(Thra和Thrb)的TH在NTIS诱导禁食或脓毒症。雄性小鼠进行48小时的禁食或盲肠结扎穿孔(CLP)诱导的脓毒症。在外周水平,禁食导致:(1)降低血清甲状腺素(T4)和三碘甲状腺原氨酸(T3),Dio 1,Thra,Slc 16 a2和MCT 8蛋白在肝脏中的表达;(2)增加肝脏Slc 16 a10和Dio 3的表达;(3)减少Slc 16 a2和Slc 16 a10在甲状腺中的表达。禁食导致垂体Tshb表达减少,下丘脑、弓状核和室旁核Dio 2表达增加。CLP诱导的脓毒症导致:(1)血清T4水平降低;(2)肝脏中Dio 1、Slc 16 a2、Slc 16 a10、Thra和Thrb表达以及甲状腺中Slc 16 a2表达降低;(3)垂体中Thrb和Tshb mRNA表达降低;(4)骨髓中总白细胞计数降低,而腹腔和胸腔积液中白细胞计数增加。总之,空腹或脓毒症驱动的NTIS通过不同的机制促进下丘脑-垂体-甲状腺轴设定点的变化。肝脏THRs表达减少与甲状腺TH转运蛋白表达减少可能分别表明外周作用和TH分泌减少,这可能导致两种模型中观察到的低TH血清水平。
Fasting and sepsis induce profound changes in thyroid hormone (TH) central and peripheral metabolism. These changes affect TH action and are called the non-thyroidal illness syndrome (NTIS). To date, it is still debated whether NTIS represents an adaptive response or a real hypothyroid state at the tissue level. Moreover, even though it has been considered the same syndrome, we hypothesized that fasting and sepsis induce a distinct set of changes in thyroid hormone metabolism. Herein, we aimed to evaluate the central and peripheral expression of genes involved in the transport (MCT8/Slc16a2 and MCT10/Slc16a10), metabolism (Dio1, Dio2, and Dio3) and action (Thra and Thrb) of TH during NTIS induced by fasting or sepsis. Male mice were subjected to a 48 h period of fasting or cecal ligation and puncture (CLP)-induced sepsis. At the peripheral level, fasting led to: (1) reduced serum thyroxine (T4) and triiodothyronine (T3), expression of Dio1, Thra, Slc16a2, and MCT8 protein in liver; (2) increased hepatic Slc16a10 and Dio3 expression; and (3) decreased Slc16a2 and Slc16a10 expressions in the thyroid gland. Fasting resulted in reduction of Tshb expression in the pituitary and increased expression of Dio2 in total hypothalamus, arcuate (ARC) and paraventricular (PVN) nucleus. CLP induced sepsis resulted in reduced: (1) T4 serum levels; (2) Dio1, Slc16a2, Slc16a10, Thra, and Thrb expression in liver as well as Slc16a2 expression in the thyroid gland (3) Thrb and Tshb mRNA expression in the pituitary; (4) total leukocyte counts in the bone marrow while increased its number in peritoneal and pleural fluids. In summary, fasting- or sepsis-driven NTIS promotes changes in the set point of hypothalamus-pituitary-thyroid axis through different mechanisms. Reduced hepatic THRs expression in conjunction with reduced TH transporters expression in the thyroid gland may indicate, respectively, reduction in the peripheral action and in the secretion of TH, which may contribute to the low TH serum levels observed in both models.
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