Phase 2 Kp-10 for Dopamine Agonist Intolerant Hyperprolactinemia IND 74,977

多巴胺激动剂不耐受高催乳素血症 2 期 Kp-10 IND 74,977

• 批准号: 10116170
• 负责人: Stephanie Beth Seminara
• 金额: $ 33.81万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116170
• 关键词: Phase; Kp; 10; Dopamine; Agonist

Abstract Hyperprolactinemia is caused by pituitary tumors and pharmacologic or pathologic interruption of dopaminergic pathways. Elevated prolactin levels can also cause endocrine dysfunction at multiple levels of the reproductive cascade including hypogonadotropic hypogonadism, irregular menstruation, erectile dysfunction, infertility and bone loss. Recent data suggests that hyperprolactinemia causes reduced kisspeptin expression, which then leads to reductions in GnRH secretion, and hypogonadotropic hypogonadism. In mice, peripheral kisspeptin administration restores GnRH secretion, gonadotropin release, and ovarian cycles. In human patients with hyperprolactinemia (Preliminary Data), exogenous kisspeptin administration also restores gonadotropin secretion. Thus, this application explores the use of exogenous pulsatile kisspeptin as a therapeutic alternative for patients with hyperprolactemia who are intolerant to current therapies.

摘要 高催乳素血症是由垂体瘤和药理学或病理学上的干扰引起的。 多巴胺能通路催乳素水平升高也可引起多个水平的内分泌功能障碍， 生殖级联反应包括低促性腺激素性功能减退、月经不调、勃起功能障碍 功能障碍、不孕症和骨质流失。最近的数据表明，高催乳素血症会导致减少 kisspeptin表达，然后导致GnRH分泌减少，和促性腺激素减退 性腺机能减退在小鼠中，外周给予kisspeptin可恢复GnRH分泌，促性腺激素释放， 卵巢周期。在高催乳素血症患者中（初步数据），外源性kisspeptin 给药也恢复促性腺激素分泌。因此，本申请探讨了使用外源性 脉冲kisspeptin作为高泌乳素血症患者的治疗选择， 目前的治疗。