Tsutsui Kazuyoshi, Son You Lee, Kiyohara Mika, Miyata Ichiro
Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Shinjuku-ku, Tokyo, Japan.
Center for Medical Life Science of Waseda University, Shinjuku-ku, Tokyo, Japan.
Endocrinology. 2018 Jan 1;159(1):62-68. doi: 10.1210/en.2017-00300.
It is known that hypothyroidism delays puberty in mammals. Interaction between the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-gonadal (HPG) axes may be important processes in delayed puberty. Gonadotropin-inhibitory hormone (GnIH) is a newly discovered hypothalamic neuropeptide that inhibits gonadotropin synthesis and release in quail. It now appears that GnIH is conserved across various mammals and primates, including humans, and inhibits reproduction. We have further demonstrated that GnIH is involved in pubertal delay induced by thyroid dysfunction in female mice. Hypothyroidism delays pubertal onset with the increase in hypothalamic GnIH expression and the decrease in circulating gonadotropin and estradiol levels. Thyroid status regulates GnIH expression by epigenetic modification of the GnIH promoter region. Furthermore, knockout of GnIH gene abolishes the effect of hypothyroidism on delayed pubertal onset. Accordingly, it is considered that GnIH is a mediator of pubertal disorder induced by thyroid dysfunction. This is a novel function of GnIH that interacts between the HPT-HPG axes in pubertal onset delay. This mini-review summarizes the structure, expression, and function of GnIH and highlights the action of GnIH in pubertal disorder induced by thyroid dysfunction.
已知甲状腺功能减退会延迟哺乳动物的青春期。下丘脑 - 垂体 - 甲状腺（HPT）轴与下丘脑 - 垂体 - 性腺（HPG）轴之间的相互作用可能是青春期延迟的重要过程。促性腺激素抑制激素（GnIH）是一种新发现的下丘脑神经肽，可抑制鹌鹑体内促性腺激素的合成和释放。现在看来，GnIH在包括人类在内的各种哺乳动物和灵长类动物中是保守的，并抑制生殖。我们进一步证明，GnIH参与雌性小鼠甲状腺功能障碍诱导的青春期延迟。甲状腺功能减退会延迟青春期开始，同时下丘脑GnIH表达增加，循环促性腺激素和雌二醇水平降低。甲状腺状态通过GnIH启动子区域的表观遗传修饰来调节GnIH表达。此外，GnIH基因敲除消除了甲状腺功能减退对青春期延迟开始的影响。因此，认为GnIH是甲状腺功能障碍诱导的青春期紊乱的介质。这是GnIH在青春期开始延迟的HPT - HPG轴之间相互作用的新功能。本综述总结了GnIH的结构、表达和功能，并强调了GnIH在甲状腺功能障碍诱导的青春期紊乱中的作用。
