甲状腺功能与生殖关系密切，GnRH神经元及上游kisspeptin神经元均有表达甲状腺激素受体，推测甲状腺激素可能直接调节生殖中枢。mTOR是细胞能量代谢状态的反映，激活的下丘脑mTOR可促进kisspeptin表达，我们前期研究发现，AMPK可介导Sp1调控下丘脑kisspeptin的转录，故推测甲状腺激素可能通过mTOR-Sp1通路调控kisspeptin的转录。本课题首先在体外观察甲状腺激素对下丘脑GT1-7细胞kisspeptin转录和表达的影响，并探讨其介导mTOR影响Sp1转位改变kisspeptin转录和表达的分子机制；然后在体内观察侧脑室内注射甲状腺激素对雌性大鼠生殖功能的影响，并观察下丘脑kisspeptin神经元特异性甲状腺受体敲除小鼠下丘脑kisspeptin的表达变化及生殖功能改变，这对揭示甲状腺功能与生殖之间的关系以及甲状腺相关的生殖疾病的防治都有重要意义。

It is known that reproductive function closely links with thyroid function. The thyroid hormone receptors were shown expressed in the GnRH neurons and its upstream neurons kisspeptin neurons, which suggesting that thyroid hormone may directly regulate genital center. mTOR is a signaling molecule reflecting the state of cellular energy metabolism, activation of hypothalamic mTOR can promote kisspeptin expression. Our previous study found that another cellular energy sensor AMPK mediated Sp1 regulation of hypothalamic kisspeptin transcription. It is speculated that thyroid hormone regulate the transcription of kisspeptin through mTOR-Sp1 in the hypothalamus. First, we would observe the effect of thyroid hormone on kisspeptin expression and transcription in the hypothalamic GT1-7 cells in vitro, and explore the molecular mechanism of Sp1 translocation mediated by mTOR. Then, the effect of thyroid hormone intracerebroventricular injection on the reproductive function of female rats would be detected in vivo. And the changes of kisspeptin expression in the hypothalamus and reproductive function of the conditional hypothalamic kisspeptin neurons thyroid receptor knockout mice would be observed. This would be of great significance to reveal the relationship between thyroid function and reproductive function, and be helpful to prevent and treat thyroid-related reproductive diseases.