The interaction between sleep and reproductive hormone secretion during puberty

青春期睡眠与生殖激素分泌之间的相互作用

• 批准号: 8510703
• 负责人: Natalie Dara Shaw
• 金额: $ 13.71万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8510703
• 关键词: 14 year old; Academic Medical Centers; Acoustic Stimulation; Adolescence; Adolescent; Adult; Affect; Aftercare; Age; Boston; Brain; Characteristics; Child; Childhood; Clinic; Clinical Investigator; Clinical Research; Complex; Continuous Positive Airway Pressure; Development Plans; Endocrine; Endocrinologist; Endocrinology; Estradiol; Follicle Stimulating Hormone; Frequencies; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Gonadotropin-Releasing Hormone Analog; Hormonal Change; Hormones; Hypothalamic structure; Integrative Medicine; Investigation; K-Series Research Career Programs; Knowledge; Link; Luteinizing Hormone; Medicine; Mentors; Modeling; Obstructive Sleep Apnea; Pediatric Hospitals; Physiologic pulse; Physiology; Pituitary Gland; Play; Polysomnography; Precocious Puberty; Protocols documentation; Proxy; Puberty; Reading; Relative (related person); Reproductive Endocrinology; Reproductive system; Research; Role; Sexual Development; Shadowing (Histology); Shapes; Sleep; Sleep Architecture; Slow-Wave Sleep; Structure; Testosterone; Time; Training; United States; Woman; boys; career; career development; design; early adolescence; experience; girls; hormone deficiency; meetings; men; normal aging; reproductive; reproductive axis; reproductive hormone; symposium; therapy design; tool; trend

DESCRIPTION (provided by applicant): At the time of puberty, the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator reawakens, stimulating pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and consequent gonadal sex steroid secretion. While it is known that the GnRH pulse generator is initially reactivated only during sleep, there has been no investigation into the underlying physiology linking the sleep and reproductive systems during puberty. My preliminary studies demonstrated an association between LH pulse initiation and deep or slow-wave sleep (SWS) in pubertal children, suggesting that a critical amount of uninterrupted sleep may be important for normal pubertal maturation. Sleep architecture changes dramatically during adolescence. There is a > 65% decline in delta power (a marker of SWS) that first occurs at age 11-12 years which is also the age of normal pubertal onset in boys and girls. While it has been hypothesized that sex steroids may play a role in shaping sleep architecture, the observational design of previous studies has precluded separation of the effects of pubertal maturation from age per se on sleep structure. Given the increasing trend of earlier sexual development in children, it is important to gain a deeper understanding of the complex interaction between sex steroids and the brain during adolescence and the potential consequences of early sex steroid exposure. This proposal will examine the critical and reciprocal interactions between sleep and the reproductive system during puberty. In Specific Aim 1, I will use a SWS disruption protocol to determine whether pulsatile secretion of LH during puberty is specifically dependent on SWS. In Specific Aim 2, I will study children with central precocious puberty before and after treatment with a GnRH analogue to investigate the effects of sex steroids on sleep architecture, independent of chronologic age. My research career development plan involves close mentoring by an experienced team of interdisciplinary clinical investigators with expertise in reproductive endocrinology, sleep medicine, and integrative physiology. I will gain formal training in sleep medicine through participation in coursework, weekly conferences, and national meetings, and will gain hands-on experience by shadowing my mentors and collaborators in sleep clinic polysomnographic reading sessions. I will continue to participate in didactic conferences in the Reproductive Endocrine Unit and at Children's Hospital Boston to expand my knowledge of endocrinology and relevant research tools. Frequent meetings with a core team of my mentors and collaborators, including Drs. Hall, Malhotra, and Butler, will help me to integrate my knowledge in sleep and reproductive endocrinology. Under a K23, I will gain the additional training in clinical research and sleep medicine that I need to attain my ultimate career goal of becoming an independent clinical investigator at an academic medical center bridging the fields of sleep medicine and pediatric reproductive endocrinology.

描述(申请人提供)：在青春期时，下丘脑促性腺激素释放激素(GnRH)脉冲发生器重新唤醒，刺激脑下垂体分泌黄体生成素(LH)和卵泡刺激素(FSH)，并随之而来的性腺类固醇分泌。虽然已知GnRH脉冲发生器最初只在睡眠期间重新激活，但尚未对青春期睡眠和生殖系统之间的潜在生理联系进行研究。我的初步研究表明，青春期儿童的黄体生成素脉冲启动与深度或慢波睡眠(SWS)之间存在关联，这表明关键的不间断睡眠对正常的青春期成熟可能是重要的。睡眠结构在青春期发生了巨大的变化。德尔塔能力(SWS的一个标志)有65%的下降，最早出现在11-12岁，这也是男孩和女孩正常青春期开始的年龄。虽然已经假设性类固醇可能在塑造睡眠结构中发挥作用，但先前研究的观察性设计排除了青春期成熟与年龄本身对睡眠结构的影响分开的可能性。鉴于儿童性发育提早的趋势越来越大，重要的是 更深入地了解青春期性激素和大脑之间的复杂相互作用，以及早期性类固醇暴露的潜在后果。这项建议将研究青春期睡眠和生殖系统之间的关键和相互作用。在特定的目标1中，我将使用SWS干扰方案来确定青春期黄体生成素的脉动性分泌是否特定地依赖于SWS。在具体目标2中，我将研究中枢性性早熟儿童使用促性腺激素释放激素类似物治疗前后的情况，以探讨性类固醇对睡眠结构的影响，与年龄无关。我的研究生涯发展计划包括由一支经验丰富的跨学科临床研究人员团队进行密切指导，他们拥有生殖内分泌学、睡眠医学和综合生理学方面的专业知识。我将通过参加课程作业、每周会议和全国会议获得正式的睡眠医学培训，并将通过跟踪我的导师和合作者在睡眠诊所多导睡眠图阅读会议中获得实践经验。我将继续参加生殖内分泌科和波士顿儿童医院的授课会议，以扩大我对内分泌学和相关研究工具的知识。经常与我的导师和合作者组成的核心团队会面，包括霍尔博士、马尔霍特拉博士和巴特勒博士，将帮助我整合我在睡眠和生殖内分泌学方面的知识。在K23学位下，我将获得临床研究和睡眠医学方面的额外培训，以实现我的最终职业目标-成为一家连接睡眠医学和儿科生殖内分泌学领域的学术医学中心的独立临床调查员。