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: 8353728
• 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/8353728
• 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. PUBLIC HEALTH RELEVANCE: The candidate for this Career Development Award is a pediatric endocrinologist studying 1) the effects of sleep disruption on reproductive hormone secretion during puberty and 2) the potential role of reproductive hormones in the changes in sleep structure that are seen across adolescence. This research will investigate whether sleep disruption, which is common in adolescence, interferes with hormone secretion and normal pubertal maturation.

描述（由申请人提供）：在青春期时，下丘脑促性腺激素释放激素（GNRH）脉搏发生器会复出，刺激性的叶酸激素（LH）和卵泡激素的垂体分泌和刺激性激素（FSH）以及促性性刺激性性别分泌。虽然众所周知，GNRH脉冲发生器最初仅在睡眠期间才重新激活，但没有研究在青春期期间与睡眠和生殖系统联系起来的潜在生理学。我的初步研究表明，在青春期儿童中LH脉冲开始与深层或慢波睡眠（SWS）之间存在关联，这表明关键的不间断睡眠可能对正常的青春期成熟可能很重要。 睡眠结构在青春期发生了巨大变化。三角洲力量（SWS的标志）在11-12岁时首次出现的增量降低了65％，这也是男孩和女孩正常青春期发作时代的年龄。尽管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从年龄本身对睡眠结构的青春期成熟作用的分离。鉴于儿童早期性发展的趋势越来越大，重要的是 在青春期期间，对性类固醇与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有了更深入的了解。 该提案将检查青春期期间睡眠与生殖系统之间的关键和相互相互作用。在特定目标1中，我将使用SWS破坏方案来确定青春期期间LH的脉冲分泌是否特别取决于SWS。在特定的目标2中，我将研究具有GNRH类似物治疗前后中心早熟青春期的儿童，以研究性类固醇对睡眠结构的影响，而与年龄无关。 我的研究职业发展计划涉及由经验丰富的跨学科临床研究人员团队的密切指导，这些研究人员在生殖内分泌，睡眠医学和综合生理学方面具有专业知识。我将通过参与课程，每周会议和全国会议获得睡眠医学的正式培训，并通过在睡眠诊所多聚会学阅读课程中遮盖我的导师和合作者，从而获得动手经验。我将继续参加生殖内分泌部门和波士顿儿童医院的教学会议，以扩大我对内分泌学和相关研究工具的了解。经常与包括DRS在内的导师和合作者组成的核心团队。霍尔（Hall），马尔霍特拉（Malhotra）和巴特勒（Butler）将帮助我整合我在睡眠和生殖内分泌学方面的知识。在K23下，我将获得临床研究和睡眠医学的额外培训，我需要实现我的最终职业目标，即成为一个学术医学中心的独立临床研究者，桥接了睡眠医学和儿科生殖内分泌学领域。 公共卫生相关性：该职业发展奖的候选人是研究的儿科内分泌学家1）睡眠中断对青春期期间生殖激素分泌的影响和2）生殖激素在整个青春期都可以看到的睡眠结构变化中的潜在作用。这项研究将调查睡眠破坏是否在青春期很常见，会干扰激素的分泌和正常的青春期成熟。