Abstract: Negative feedback regulation in the hypothalamic-pituitary-thyroid (HPT) axis primarily functions to maintain normal and circulating levels of thyroid hormone (TH). Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus are believed to represent the regulatory core of the HPT axis. Studies have showed that not only circulating triiodothyronine (T3), tetraiodothyronine (T4) could also regulate intracellular T3 availability by type 2 deiodinase (Dio2) in tanycytes and responsible for negative feedback regulation of hypophysiotropic TRH. TH was transported into the hypophysiotropic TRH neurons by TH transporters and bound to thyroid hormone receptors (TRs), especially TRβ2, with the recruitment of coregulators by the TRs, participating in regulation of the corresponding target gene. In addition, tanycytes have been shown to express pyroglutamyl peptidase II (PPII), which degraded TRH releasing from TRH neurons and furthermore affected the TRH concentration in portal blood in different thyroid states. This article summarized molecular components of HPT axis regulation, which was aimed to provide reference for the scientific researches and clinical treatment of thyroid dysfunction or HPT axis abnormalities.

Key words: HPT axis, negative feedback, thyroid hormone, deiodinase

摘要： 下丘脑-垂体-甲状腺（hypothalamic-pituitary-thyroid，HPT）轴负反馈调节是维持血清甲状腺激素（thyroid hormone,TH）水平稳定的最重要的机制。目前，普遍认为位于下丘脑室旁核（paraventricular nuclei,PVN）的促垂体区的促甲状腺激素释放激素（thyrotropin-releasing hormone,TRH）神经元是HPT轴的核心调节区域。研究认为在血液循环中，不仅三碘甲状腺原氨酸（T3）参与HPT轴的负反馈调节，甲状腺素（T4）也可通过中枢神经系统伸长细胞的脱碘酶2（Dio2）催化脱碘来影响细胞中T3的可用性，从而参与其中。促垂体区的TRH神经元通过甲状腺激素转运体摄取循环中的TH，而TH进入PVN的TRH神经元或垂体促甲状腺区细胞核与甲状腺激素受体（TRs）（特别是TRβ2）结合后，可招募辅因子，共同参与相应靶基因的调控。此外，中枢神经系统伸长细胞表达的焦谷氨酰肽酶Ⅱ（PPⅡ）可降解释放的TRH，从而影响不同甲状腺功能状态下到达垂体门静脉的TRH水平。综述了参与HPT轴调节的分子元件，以期为甲状腺功能或甲状腺轴异常疾病的科学研究及临床治疗提供参考。

关键词: HPT轴, 负反馈, 甲状腺激素, 脱碘酶