Mireille L'Hermite-Balériaux

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.

Phase‐shifts of 24‐h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men

Objective  Older adults are less responsive to the phase‐shifting effects of light than younger subjects and may have difficulties adapting to abrupt time shifts. This study aims to determine whether the potent melatonin agonist agomelatine (S‐20098) is capable of phase‐shifting overt circadian rhythms in older adults.

Acute and Delayed Effects of Exercise on Human Melatonin Secretion

Accumulating evidence suggests that exercise may have both rapid and delayed effects on human melatonin secretion. Indeed, exercise may acutely (i.e., within minutes) alter melatonin levels and result in a shift of the onset of nocturnal melatonin 12 to 24 h later. The presence and nature of both acute and delayed effects appear to be dependent on the timing of exercise. The presence of a detectable acute effect also depends on the duration, intensity, and type of exercise. Late evening exercise during the rising phase of melatonin secretion may blunt melatonin levels. High-intensity exercise during the nighttime period, when melatonin levels already are elevated, consistently results in a further (nearly 50%) elevation of melatonin levels. No effect of low-intensity exercise performed at the same circadian phase could be detected. Irrespective of intensity, exercise near the offset of melatonin secretion or during the daytime has no consistent acute effect on melatonin secretion. Nighttime exercise, whether of moderate or high intensity, results in phase delays of the melatonin onset on the next evening. In support of the concept that a shift of the melatonin onset on the day after nighttime exercise represents a shift of intrinsic circadian timing is the observation that similar phase shifts (in both direction and magnitude) may be observed simultaneously for the onset of the circadian elevation of thyrotropin secretion. The observation of exercise-induced phase shifts of the onset of melatonin secretion is, therefore, interpreted as evidence that, in humans as in rodents, increased physical activity during the habitual rest period is capable of altering circadian clock function.

Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

CONTEXT Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. OBJECTIVE Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. METHODS Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. RESULTS Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. CONCLUSION The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

Effects of exercise on neuroendocrine secretions and glucose regulation at different times of day

To study the effects of time of day on neuroendocrine and metabolic responses to exercise, body temperature, plasma glucose, insulin secretion rates (ISR), and plasma cortisol, growth hormone (GH) and thyrotropin (TSH) were measured in young men, both at bed rest and during a 3-h exercise period (40-60% maximal O2 uptake). Exercise was performed at three times of day characterized by marked differences in cortisol levels, i.e., early morning (n = 5), afternoon (n = 8), and around midnight (n = 9). The subjects were kept awake and fasted, but they received a constant glucose infusion to avoid hypoglycemia. Exercise-induced elevations of temperature were higher in the early morning than at other times of day. The exercise-induced glucose decrease was approximately 50% greater around midnight, when cortisol was minimal and not stimulated by exercise, than in the afternoon or early morning (P < 0.05). This effect of time of day appeared unrelated to decreases in ISR or increases in temperature and GH. Robust TSH increases occurred in all exercise periods and were maximal at night. The results demonstrate the existence of circadian variations in neuroendocrine and metabolic responses to exercise.To study the effects of time of day on neuroendocrine and metabolic responses to exercise, body temperature, plasma glucose, insulin secretion rates (ISR), and plasma cortisol, growth hormone (GH) and thyrotropin (TSH) were measured in young men, both at bed rest and during a 3-h exercise period (40-60% maximal O2uptake). Exercise was performed at three times of day characterized by marked differences in cortisol levels, i.e., early morning ( n = 5), afternoon ( n = 8), and around midnight ( n = 9). The subjects were kept awake and fasted, but they received a constant glucose infusion to avoid hypoglycemia. Exercise-induced elevations of temperature were higher in the early morning than at other times of day. The exercise-induced glucose decrease was ∼50% greater around midnight, when cortisol was minimal and not stimulated by exercise, than in the afternoon or early morning ( P < 0.05). This effect of time of day appeared unrelated to decreases in ISR or increases in temperature and GH. Robust TSH increases occurred in all exercise periods and were maximal at night. The results demonstrate the existence of circadian variations in neuroendocrine and metabolic responses to exercise.

Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study.

Dehydroepiandrosterone (DHEA) administration is widely evocated as a ‘fountain of youth’, but previous studies have provided inconsistent results. We aimed to investigate in healthy postmenopausal women the effects of a 3‐week oral DHEA administration on individual steroid levels, multiple 24‐h hormonal profiles and sleep architecture.

Growth hormone and the aging male

Growth hormone (GH) exerts a crucial role in promoting somatic growth. In addition, GH constitutes a major regulator of body composition, bone and muscle metabolism, and cardiac function, and actually acts as a prime modulator of fuel metabolism. GH secretion is maximal during puberty. Thereafter, GH secretion falls in young adulthood to less than half the values achieved in mid- to late puberty. This decline is exponential, with a t1/12 of approximately 7 years, and is essentially complete by the beginning of the fifth decade. The origin of this decrease is likely to be multifactorial but the underlying mechanisms remain largely speculative. Since aging and ‘true’ GH deficiency due to pituitary disorders are associated with similar somatic features, it has been suggested that in older healthy subjects, these features result from relative GH-insulin-like growth factor-I (IGF-I) deficit and represent a syndrome that has been named somatopause. So far, however, the causal link between these somatic features...