Basic and Clinical Studies on Humoral Control of Sleep

从以下两个方面探讨了睡眠机制的体液调控：1)Delta型睡眠诱导肽(DSIP)作为慢波促进物质的可能作用；2)生长激素(GH)在慢波睡眠(SWS)中的分泌模式。这种方法无法在人和大鼠组织中检测到DSIP样物质。对健康男性受试者血浆DSIP浓度进行了连续24小时的测定，发现循环中DSIP浓度存在昼夜变化。除了已知的促进睡眠作用外，我们还在大鼠身上发现了DSIP的体温调节作用。在常温下，DSIP及其磷酸化形式(P-DSIP)被发现能增强多巴胺或5-羟色胺诱导的大鼠体温下降。药理研究表明，DSIP的这种体温调节作用是通过5-HT1A受体实现的。佐匹克隆是一种非苯二氮类催眠药，已证实可增加…大鼠脑内Se-DSIP含量增加，呈剂量依赖关系。这些发现可能进一步表明DSIP在调节睡眠和睡眠相关现象中的重要作用。我们引入了一种超灵敏的人生长激素EIA方法来评估正常条件下和睡眠剥夺条件下的24小时分泌模式。基础血浆生长激素的最低水平为10pg/ml，这是首次用该方法检测到的。正常睡眠期和延迟睡眠期的24小时生长激素分泌节律提示生长激素分泌存在超常节律。在同一样本中还检测了催乳素和促甲状腺激素(TSH)。发现催乳素在睡眠中升高，在快速眼动睡眠后，催乳素的分泌似乎被促进。此外，通过在5分钟间隔内频繁测定血浆GH和催乳素，更详细地研究了激素分泌与第一次SWS启动之间的关系。SWS开始后10min，GH分泌增加，催乳素分泌模式与GH分泌模式基本一致。也就是说，GH分泌、催乳素分泌和第一次SWS过程以某种方式彼此同步，但有很短的延迟。TSH分泌有其自身的分泌模式，夜间分泌较高，一般受睡眠抑制。较少

The humoral control of sleep mechanisms was investigated in terms of 1) possible roles of delta sleep-inducing peptide (DSIP) as one of slow-wave promoting substances, and 2) secretary pattern of growth hormone (GH) during slow wave sleep (SWS).A sensitive enzyme immunoassay (EIA) method for measuring DSIP in body fluids was developed in the laboratory. This method was unable to detect DSIP-like material in human and rat tissues. Plasma DSIP levels were measured throughout 24 h in healthy male subjects and diurnal variations of circulatory DSIP concentrations were found. Besides its known sleep-promoting effect, we found the thermoregulatory action of DSIP in rats. DSIP as well as its phosphorylated form (P-DSIP) was found to potentiate dopamine- or serotonin-induced hypothermia in rats at the ambient temperature. Pharmacological study showed this thermoregulatory action of DSIP was exerted via 5-HT 1A receptors. Zopiclone, one of non-benzodiazepine hypnotics was demonstrated to increa … More se DSIP contents in the rat brain dose-dependently. These findings may further present significant roles of DSIP in modulating sleep and sleep-related phenomena.An ultra-sensitive EIA method of human GH was introduced to evaluate 24 h secretary pattern in normal condition and in sleep-deprived condition. The lowest level of basal plasma GH was as low as 10 pg/ml, which could be detected for the first time by this method. Twenty-four hour secretory rhythm of GH in normal and delayed sleep phase suggested the presence of ultradian rhythm in GH secretion. Prolactin and thyroid-stimulating hormone (TSH) were also measured in the same samples. Prolactin was found to be elevated during sleep and prolactin secretion appeared to be promoted after REM sleep. Furthermore, the relationship between hormone secretion and initiation of the first SWS was studied in more detail by frequent determinations of plasma GH and prolactin in 5-min intervals. GH secretion increased 10 min after the initiation of SWS, and the pattern of prolactin secretion was found to be almost identical with GH secretion. Namely, GH secretion, prolactin secretion and the first SWS processes were somehow synchronized one another with a short delay. TSH secretion had its own secretory pattern with higher values during night, which normally was inhibited by sleep. Less