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

• 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
• 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

 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.