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

Kisspeptin 和 Neurokinin B：从猴子的生理学到人类的病理生理学

基本信息

批准号：
9431349
负责人：
Stephanie Beth Seminara
金额：
$ 8.36万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-23 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9431349
关键词：
Address Adolescence Adolescent Adult Agonist Animals Architecture Biological Assay Brain Child Childhood Clinic Collaborations Consensus Constitutional Delayed Puberty Development Diagnostic Disease Dynorphins Functional disorder GNRH1 gene Gatekeeping Generations Genes Genetic Gonadal Steroid Hormones Grant Hormones Human Hypothalamic structure KISS1 gene Kallmann Syndrome Learning Liquid substance Macaca mulatta Male Adolescents Monkeys Mutation Neurokinin B Neurons Neuropeptides Neurosecretory Systems Patients Peptides Pharmacology Physiologic pulse Physiological Physiology Positioning Attribute Primates Puberty Recovery Research Personnel Role Sexual Maturation Signal Transduction Substance P Testosterone Translating Work boys experience human male in vivo insight interdisciplinary collaboration male man nonhuman primate novel novel diagnostics outcome prediction predictive tools public health relevance receptor reproductive reproductive development research study response tool

项目摘要

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.

描述（由申请人提供）：Kisspeptin和神经激肽B都是生殖成熟的关键守门人，但关于这些神经肽如何刺激GnRH分泌仍有很多需要了解的内容。这项拨款将锚之间的合作，两个调查人员独特的定位，以研究这些肽在非人类灵长类动物和人类在体内的生理学。在雄性猴中，将使用新型试验和受体激动剂和拮抗剂探索kisspeptin和NKB对整个青春期GnRH分泌的贡献。在成年男性中，将评估特发性低促性腺激素性性腺功能减退症（IHH）患者的外源性kisspeptin给药作为GnRH脉冲分泌自发恢复的预测工具。在青春期男性中，将探索外源性kisspeptin作为区分体质性青春期延迟（CDP）和IHH的诊断工具。通过专注于青春期的过渡，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。