权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

甲状腺ホルモンによる生殖制御におけるＧｎＩＨシステムの作用機構

GnIH系统在甲状腺激素生殖控制中的作用机制

基本信息

批准号：
15F15909
负责人：
筒井和義
金额：
$ 1.47万
依托单位：
Waseda University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2015
资助国家：
日本
起止时间：
2015-04-24 至 2017-03-31
项目状态：
已结题

项目摘要

Thyroid disorders lead to abnormal pubertal development. Although interactions between the thyroid and reproductive endocrine systems are suggested, the detailed mechanisms of how thyroid hormone influences pubertal onset remain unclear. The hypothalamic peptide, gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the possible role of GnIH on pubertal onset. Therefore, we investigated the involvement of GnIH in thyroid status-induced pubertal disorders.To do this, we induced hypothyroidism and hyperthyroidism in juvenile female mice, then analyzed the change in the regulatory factors of the reproductive axis. Hypothyroidism showed delayed pubertal onset with increased GnIH expression, however hypothyroidism-induced delayed puberty was prevented by GnIH-knockout, suggesting that GnIH may mediate the effect of hypothyroidism on pubertal delay. Reversely, hyperthyroidism had no effect on pubertal onset, however GnIH expression was significantly decreased, indicating the negative correlation between thyroid status and GnIH expression. Further, we found that hypothalamic GnIH neurons express thyroid hormone receptors (TRs), which may convey thyroid hormone signals directly to GnIH neurons. Although TRs did not directly bind to GnIH promoter region, thyroid status actively altered the chromatin modifications in GnIH promoter region.Our findings indicate a novel function of GnIH to mediate the cross-talk between the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-gonadal axes in proper pubertal development.

甲状腺疾病导致青春期发育异常。虽然甲状腺和生殖内分泌系统之间的相互作用的建议，甲状腺激素如何影响青春期开始的详细机制仍不清楚。下丘脑肽促性腺激素抑制激素（GnIH）被证明是减少在青春期前的早期阶段，提示GnIH的青春期开始的可能作用。因此，我们研究了GnIH在甲状腺状态引起的青春期疾病中的作用，为此，我们在幼年雌性小鼠中诱导甲状腺功能减退和甲状腺功能亢进，然后分析生殖轴调节因子的变化。甲状腺功能减退症表现出延迟青春期的发病与GnIH表达增加，但甲状腺功能减退症引起的青春期延迟被阻止GnIH基因敲除，提示GnIH可能介导甲状腺功能减退症对青春期延迟的影响。然而，甲状腺功能亢进对青春期的开始没有影响，但GnIH表达显著降低，表明甲状腺状态与GnIH表达呈负相关。此外，我们发现，下丘脑GnIH神经元表达甲状腺激素受体（TRs），它可以直接将甲状腺激素信号传递给GnIH神经元。虽然TRs不直接与GnIH启动子区结合，但甲状腺状态可主动改变GnIH启动子区的染色质修饰，提示GnIH在青春期正常发育过程中介导下丘脑-垂体-甲状腺轴和下丘脑-垂体-性腺轴之间的相互作用。