Kisspeptin and Neurokinin B: Physiology in Monkey to Pathophysiology in Human

 描述(申请人提供)：Kispeptin和Neurkinin B都是生殖成熟的关键看门人，但关于这些神经肽如何刺激GnRH分泌仍有许多需要了解。这笔赠款将巩固两名研究人员之间的合作，这两名研究人员在研究这些肽在非人类灵长类动物和活体人类中的生理学方面具有独特的地位。在雄性猴子中，将使用新的分析方法以及受体激动剂和拮抗剂来探索Kispeptin和NKB对青春期GnRH分泌的贡献。在成年男性中，对特发性低促性腺激素减退症(IHH)患者应用外源性Kispeptin将被评估为一种预测GnRH脉动性分泌自发恢复的工具。在青春期男性中，外源性Kispeptin将被探索作为区分体质青春期延迟(CDP)和IHH的诊断工具。通过关注青春期的转变，并结合正常和病理生理状态，这笔赠款将发展对生殖成熟的见解，并开发青春期疾病的诊断工具。

 DESCRIPTION (provided by applicant): Kisspeptin and neurokinin B are both critical gatekeepers for reproductive maturation but there is still much to learn about how these neuropeptides stimulate GnRH secretion. This grant will anchor a collaboration between two investigators uniquely positioned to study the physiology of these peptides in non-human primates and humans in vivo. In the male monkey, the contributions of kisspeptin and NKB to GnRH secretion will be explored across puberty using novel assays and receptor agonists and antagonists. In the adult human male, exogenous kisspeptin administration to patients with idiopathic hypogonadotropic hypogonadism (IHH) will be assessed as a predictive tool for spontaneous recovery of GnRH pulsatile secretion. In the adolescent human male, exogenous kisspeptin will be explored as a diagnostic tool to distinguish between constitutional delay of puberty (CDP) and IHH. By focusing on the pubertal transition, and incorporating normal and pathophysiologic states, this grant will develop insights into reproductive maturation and develop diagnostic tools for pubertal disorders.