Terasawa Ei, Garcia James P, Seminara Stephanie B, Keen Kim L
Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, United States.
Department of Pediatrics, University of Wisconsin, Madison, WI, United States.
Front Endocrinol (Lausanne). 2018 Apr 6;9:148. doi: 10.3389/fendo.2018.00148. eCollection 2018.
In human patients, loss-of-function mutations in the genes encoding kisspeptin () and neurokinin B ( and their receptors ( and , respectively) result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the hypothalamus with infusion of agonists and antagonists for kisspeptin and NKB reveal that kisspeptin and NKB signaling stimulate GnRH release independently or collaboratively by forming kisspeptin and NKB neuronal networks depending on the developmental age. For example, while in prepubertal females, kisspeptin and NKB signaling independently stimulate GnRH release, in pubertal females, the formation of a collaborative kisspeptin and NKB network further accelerates the pubertal increase in GnRH release. It is speculated that the collaborative mechanism between kisspeptin and NKB signaling to GnRH neurons is necessary for the complex reproductive function in females.
在人类患者中，编码 kisspeptin（）和神经激肽 B（及其受体（分别为 和 ）的基因功能丧失突变会导致青春期时间异常或青春期缺失。为了解青春期的神经内分泌机制，我们以恒河猴为模型，研究了 kisspeptin 和 NKB 信号对青春期 GnRH 释放增加的作用。通过在下丘脑正中隆起处直接测量 GnRH 和 kisspeptin，并注入 kisspeptin 和 NKB 的激动剂和拮抗剂，结果显示，根据发育年龄，kisspeptin 和 NKB 信号通过形成 kisspeptin 和 NKB 神经元网络独立或协同刺激 GnRH 释放。例如，在青春期前的雌性中，kisspeptin 和 NKB 信号独立刺激 GnRH 释放，而在青春期雌性中，协同的 kisspeptin 和 NKB 网络的形成进一步加速了 GnRH 释放的青春期增加。据推测，kisspeptin 和 NKB 信号对 GnRH 神经元的协同机制对于雌性复杂的生殖功能是必要的。
