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

描述（由申请人提供）：男孩和女孩青春期的最早生理体征是下丘脑促性腺激素释放激素（GnRH）和垂体黄体生成素（LH）的脉动性分泌增加。这种增强最初只在睡眠时发生。我们假设阻塞性睡眠呼吸暂停（OSA）患儿的缺氧发作和觉醒会破坏青春期早期OSA患儿夜间GnRH/LH分泌模式。具体来说，我们预计在青春期早期患有OSA的儿童，其LH脉冲频率和幅度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名接受持续气道正压通气（CPAP）机治疗的青春期早期OSA儿童。每个孩子将接受两项研究，包括一项多导睡眠图睡眠研究，同时频繁抽血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，确定在没有CPAP的情况下LH脉冲频率和幅度是否下降。然后，我们将研究在无缺氧情况下的脑电图唤醒是否会产生LH脉冲频率和幅度的衰减。我们将再招募15名儿童，每个儿童将接受两次多导睡眠图睡眠研究，并频繁抽血。CPAP将在两项研究中使用，其中一项研究将使用听觉刺激诱导脑电图唤醒。研究的顺序将随机化。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在儿童中的高患病率（1-4%），大量儿童可能存在生殖功能障碍风险，表现为发育不全或发育迟缓。这些研究将使我们能够定义这种风险，并为GnRH/LH脉冲与睡眠的基本生理学提供更深入的见解。

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.