Laurence Plat

Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men.

The aim of this study was to investigate, in normal young men, whether gamma-hydroxybutyrate (GHB), a reliable stimulant of slow-wave (SW) sleep in normal subjects, would simultaneously enhance sleep related growth hormone (GH) secretion. Eight healthy young men participated each in four experiments involving bedtime oral administration of placebo, 2.5, 3.0, and 3.5 g of GHB. Polygraphic sleep recordings were performed every night, and blood samples were obtained at 15-min intervals from 2000 to 0800. GHB effects were mainly observed during the first 2 h after sleep onset. There was a doubling of GH secretion, resulting from an increase of the amplitude and the duration of the first GH pulse after sleep onset. This stimulation of GH secretion was significantly correlated to a simultaneous increase in the amount of sleep stage IV. Abrupt but transient elevations of prolactin and cortisol were also observed, but did not appear to be associated with the concomitant stimulation of SW sleep. Thyrotropin and melatonin profiles were not altered by GHB administration. These data suggest that pharmacological agents that reliably stimulate SW sleep, such as GHB, may represent a novel class of powerful GH secretagogues.

Alterations of Circadian Rhythmicity and Sleep in Aging: Endocrine Consequences

All 24-hour endocrine rhythms partially reflect the interaction of circadian rhythmicity with sleep-wake homeostasis but their relative contributions vary from one system to another. In older adults, many 24-hour rhythms are dampened and/or advanced, including those of cortisol and GH. Amplitude reduction and phase advance of 24-hour rhythms may represent age-related changes in the central nervous systems underlying circadian rhythmicity and sleep-wake homeostasis. Age-related alterations in circadian function could also reflect decreased exposure and/or responsivity to the synchronizing effects of both photic (e.g. light exposure) and nonphotic (e.g. social cues) inputs. There are pronounced age-related alterations in sleep quality in aging which consist primarily of a marked reduction of slow-wave sleep, a reduction in REM stages and a marked increase in the number and duration of awakenings interrupting sleep. Alterations in slow-wave sleep occur abruptly in young adulthood (30–40 years of age) whereas disturbances in amounts of REM and wake appear more gradually. This article reviews evidence indicating that deficits in characteristics of sleep-wake homeostasis and circadian function may mediate age-related alterations in somatotropic and corticotropic function. Because sleep loss in young subjects results in endocrine disturbances which mimic those observed in aging, it is conceivable that the decrease in sleep quality which characterizes aging may contribute to age-related alterations in hormonal function and their metabolic consequences.

Physiology of growth hormone secretion during sleep

The temporal relation between the first few hours of sleep and the secretion of growth hormone (GH), which is present in normal persons of both sexes from early childhood until late adulthood, is reviewed. In adults the most reproducible pulse of GH secretion occurs shortly after the onset of sleep in association with the first phase of slow-wave sleep (SWS) (stages III and IV). In men approximately 70% of the GH pulses during sleep coincide with SWS, and the amount of GH secreted during these pulses correlates with the concurrent amount of SWS. Sleep-related secretion of GH appears to be primarily dependent on the release of growth hormone-releasing-hormone. Rodent and human studies have shown that growth hormone-releasing hormone injections decrease wakefulness and increase SWS. During the fourth decade of life (ages 30 to 40 years) the total amount of GH secreted over a 24-hour span decreases by two- to threefold. Similarly, the amount of SWS decreases dramatically over the same narrow age range. Because the sleep-onset GH pulse is often the major secretory output in adults, age-related decrements in sleep-related GH secretion likely play a major role in the hyposomatotropism of senescence.