Effect of sleep apnea on nocturnal GnRH/LH secretion in children in early puberty

睡眠呼吸暂停对青春期早期儿童夜间GnRH/LH分泌的影响

• 批准号: 7912560
• 负责人: Natalie Dara Shaw
• 金额: $ 6.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7912560
• 关键词: Arousal; Blood specimen; Child; Childhood; Continuous Positive Airway Pressure; Electroencephalography; Endocrinologist; Enrollment; Failure; Frequencies; Functional disorder; Gonadotropin Hormone Releasing Hormone; Gonadotropins; High Prevalence; Hypothalamic structure; Hypoxia; Luteinizing Hormone; Obstructive Sleep Apnea; Pattern; Physiologic pulse; Physiological; Physiology; Pituitary Gland; Polysomnography; Population; Protocols documentation; Puberty; Randomized; Research; Risk; Severities; Sleep; Sleep Apnea Syndromes; Sleep Stages; Staging; Supervision; auditory stimulus; boys; girls; insight; public health relevance; reproductive

DESCRIPTION (provided by applicant): The earliest physiological sign of puberty in both boys and girls is an augmentation of the pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH). This augmentation initially occurs only during sleep. We hypothesize that the hypoxic episodes and arousals which disrupt sleep in children with obstructive sleep apnea (OSA) will disrupt the nocturnal GnRH/LH secretory pattern of children with OSA in the early stages of puberty. Specifically, we expect children with OSA in early puberty to have decreased LH pulse frequency and amplitude proportional to the severity of their sleep apnea. To investigate this hypothesis, we will enroll 15 children in early puberty with OSA treated with a continuous positive airway pressure (CPAP) machine. Each child will undergo two studies consisting of a polysomnographic sleep study with simultaneous frequent blood sampling to detect LH pulses with or without CPAP in random order such that each child serves as his own control to determine whether LH pulse frequency and amplitude are decreased in the absence of CPAP. We will then investigate whether EEG arousals in the absence of hypoxia can produce a decrement in LH pulse frequency and amplitude. We will enroll another 15 children, and each child will undergo two polysomnographic sleep studies with frequent blood sampling. CPAP will be used in both studies during one of which auditory stimuli will be used to induce EEG arousals. The order of the studies will be randomized. These protocols will also allow us to analyze the connection between sleep stage and GnRH/LH pulses during puberty. Given the high prevalence of OSA in children (1-4%), there is a potentially large population of children at risk for reproductive dysfunction in the form of failure to progress or delayed progression through puberty. These studies will allow us to define this risk as well as to provide greater insights into the basic physiology which ties GnRH/LH pulses to sleep. PUBLIC HEALTH RELEVANCE: This research will determine if the relatively large population of children with OSA is at risk for failure to progress or delayed progression through puberty and would therefore benefit from the close supervision of a pediatric endocrinologist.

描述（由申请人提供）：男孩和女孩青春期最早的生理标志是下丘脑促性腺激素释放激素（GnRH）和垂体黄体生成素（LH）的脉冲式分泌增加。这种增强最初仅发生在睡眠期间。我们假设，扰乱阻塞性睡眠呼吸暂停 (OSA) 儿童睡眠的缺氧发作和觉醒会扰乱青春期早期 OSA 儿童的夜间 GnRH/LH 分泌模式。具体来说，我们预计青春期早期患有 OSA 的儿童 LH 脉冲频率和幅度的降低与睡眠呼吸暂停的严重程度成正比。为了研究这一假设，我们将招募 15 名患有 OSA 的青春期早期儿童，并使用持续气道正压通气 (CPAP) 机进行治疗。每个孩子将接受两项研究，包括多导睡眠图睡眠研究，同时频繁进行血液采样，以随机顺序检测有或没有 CPAP 的 LH 脉冲，以便每个孩子作为自己的对照，以确定在没有 CPAP 的情况下 LH 脉冲频率和幅度是否降低。然后我们将研究在没有缺氧的情况下脑电图唤醒是否会导致 LH 脉冲频率和幅度减少。我们将招募另外 15 名儿童，每个儿童将接受两次多导睡眠研究并频繁采血。这两项研究都将使用 CPAP，其中一项研究将使用听觉刺激来诱导脑电图唤醒。研究的顺序将是随机的。这些协议还将使我们能够分析青春期睡眠阶段和 GnRH/LH 脉冲之间的联系。鉴于 OSA 在儿童中的患病率较高（1-4%），大量儿童可能面临青春期发育迟缓或进展迟缓等生殖功能障碍的风险。这些研究将使我们能够定义这种风险，并为将 GnRH/LH 脉冲与睡眠联系起来的基本生理学提供更深入的见解。 公共卫生相关性：这项研究将确定相对较多的 OSA 儿童是否存在青春期进展失败或进展延迟的风险，因此是否会受益于儿科内分泌学家的密切监督。