3-Iodothyronamine Induces Tail Vasodilation Through Central Action in Male Mice
3-Iodothyronamine Induces Tail Vasodilation Through Central Action in Male Mice
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DOI：
10.1210/en.2016-1951
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发表时间：
2017-06-01
期刊：
影响因子：
4.8
通讯作者：
Mittag, Jens
中科院分区：
文献类型：
--
作者：
Gachkar, Sogol;Oelkrug, Rebecca;Mittag, Jens
3-碘甲腺原氨酸（3-T1 AM）是一种内源性甲状腺激素（TH）衍生的代谢产物，全身给药后可诱导小鼠出现严重的体温过低;然而，其潜在机制仍然是个谜。我们在这里表明，3-T1 AM诱导的体温快速下降是外周血管舒张和随后的热量损失的结果（例如，在尾部表面上）。这种情况随后因运动不足和缺乏棕色脂肪组织激活而加剧。尽管在尾动脉和主动脉中分别检测到可能的3-T1 AM靶点痕量胺相关受体1或α 2a-肾上腺素能受体，但肌电研究未显示3-T1 AM对血管舒张的任何直接作用，表明其作用可能是间接的。然而，脑室内应用3-T1 AM复制了尾部血管舒张和体温下降的表型，并导致下丘脑神经元活化，表明代谢产物通过下丘脑信号传导途径引起尾部血管舒张。因此，3-T1 AM反应构成了发热而不是体温过低，并且非常类似于由下丘脑温度敏感神经元介导的热应激反应。因此，我们的研究结果强调了下丘脑作为人体恒温器的众所周知的作用，并提出了TH信号传导和体温的中央控制之间的额外分子联系。
3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone (TH)-derived metabolite that induces severe hypothermia in mice after systemic administration; however, the underlying mechanisms have remained enigmatic. We show here that the rapid 3-T1AM-induced loss in body temperature is a consequence of peripheral vasodilation and subsequent heat loss (e.g., over the tail surface). The condition is subsequently intensified by hypomotility and a lack of brown adipose tissue activation. Although the possible 3-T1AM targets trace amine-associated receptor 1 or alpha 2a-adrenergic receptor were detected in tail artery and aorta respectively, myograph studies did not show any direct effect of 3-T1AM on vasodilation, suggesting that its actions are likely indirect. Intracerebroventricular application of 3-T1AM, however, replicated the phenotype of tail vasodilation and body temperature decline and led to neuronal activation in the hypothalamus, suggesting that the metabolite causes tail vasodilation through a hypothalamic signaling pathway. Consequently, the 3-T1AM response constitutes anapyrexia rather than hypothermia and closely resembles the heat-stress response mediated by hypothalamic temperature-sensitive neurons. Our results thus underline the well-known role of the hypothalamus as the body's thermostat and suggest an additional molecular link between TH signaling and the central control of body temperature.