KiSS-1/GPR54 and the Reproductive Neuroendocrine Axis

KiSS-1/GPR54 和生殖神经内分泌轴

• 批准号: 6884315
• 负责人: Michelle L Gottsch
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884315
• 关键词: cell surface receptors; genetically modified animals; gonadotropins; human puberty; hypogonadism; immunocytochemistry; in situ hybridization; laboratory mouse; ligands; messenger RNA; neuroendocrine system; neuropeptide receptor; postdoctoral investigator; reproductive system; tumor suppressor genes

DESCRIPTION (provided by applicant): Humans and mice having dysfunctional mutations in the G-coupled receptor GPR54 have low gonadotropin levels and thus fail to undergo normal pubertal maturation. KiSS-1 gene products, known as kisspeptins, are thought to be the endogenous ligands for GPR54. KiSS-1 and GPR54 are expressed in areas of the forebrain that control reproduction and centrally-administered kisspeptins stimulate gonadotropin secretion in the rodent and primate. These observations suggest that activation of GPR54 is essential for the normal progression of pubertal development and the maintenance of reproductive function in the adult. The goal of this project is to elucidate the role of the KiSS-1 gene products (particularly Mestatin) and GPR54 in the neuroendocrine reproductive axis, focusing on their possible role in the negative and positive feedback control of gonadotropin secretion by sex steroids and in determining the onset of puberty. Elucidating the functional significance of Mestatin and GPR54 in the control of reproduction should provide further insight into the mechanisms responsible for idiopathic hypogonadotropic hypogonadism in humans and could provide scientific rationale for new therapies to treat precocious or delayed puberty and infertility.

描述（由申请人提供）：在G偶联受体GPR 54中具有功能障碍性突变的人和小鼠具有低促性腺激素水平，因此不能经历正常的青春期成熟。KiSS-1基因产物，称为kisspeptins，被认为是GPR 54的内源性配体。KiSS-1和GPR 54在控制生殖的前脑区域中表达，并且集中施用的kisspeptins刺激啮齿动物和灵长类动物的促性腺激素分泌。这些观察结果表明，GPR 54的激活对于青春期发育的正常进展和成年生殖功能的维持是必不可少的。该项目的目标是阐明KiSS-1基因产物（特别是Mestatin）和GPR 54在神经内分泌生殖轴中的作用，重点是它们在性类固醇促性腺激素分泌的负反馈和正反馈控制中的可能作用，以及决定青春期的开始。阐明Mestatin和GPR 54在控制生殖方面的功能意义，应能进一步了解人类特发性低促性腺激素性性腺功能减退症的机制，并为治疗性早熟或青春期延迟和不孕症的新疗法提供科学依据。