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

描述（由申请人提供）：男孩和女孩青春期最早的生理体征是下丘脑促性腺激素释放激素（GnRH）和垂体促黄体激素（LH）的脉冲式分泌增加。这种增强最初只发生在睡眠期间。我们假设，缺氧发作和觉醒，扰乱睡眠阻塞性睡眠呼吸暂停（OSA）儿童的睡眠将扰乱夜间GnRH/LH分泌模式的OSA儿童在青春期的早期阶段。具体来说，我们预计青春期早期OSA儿童LH脉冲频率和幅度的降低与其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名青春期早期的OSA儿童，他们接受持续气道正压通气（CPAP）机治疗。每名儿童将接受两项研究，包括多导睡眠图睡眠研究，同时频繁采血，以随机顺序检测是否存在CPAP的LH脉冲，以便每名儿童作为自己的对照，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，我们将研究是否在缺氧的情况下，脑电图唤醒可以产生LH脉冲频率和幅度的递减。我们将招募另外15名儿童，每个儿童将接受两次多导睡眠图睡眠研究，并频繁采血。CPAP将用于两项研究，其中一项研究将使用听觉刺激诱导EEG觉醒。研究顺序将随机化。这些协议也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在儿童中的高患病率（1-4%），存在潜在的大量儿童处于生殖功能障碍的风险中，其形式为青春期进展失败或延迟进展。这些研究将使我们能够定义这种风险，并对将GnRH/LH脉冲与睡眠联系在一起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大的OSA儿童人群是否存在青春期进展失败或延迟进展的风险，因此将受益于儿科内分泌学家的密切监督。

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.