Biomedical subjects

R Leproult

Publications and source records attributed to R Leproult.

28 records · Page 2Linked to original sources

PubMed1997

Sleep loss results in an elevation of cortisol levels the next evening.

Sleep curtailment constitutes an increasingly common condition in industrialized societies and is thought to affect mood and performance rather than physiological functions. There is no evidence for prolonged or delayed effects of sleep loss on the hypothalamo-pituitary-adrenal (HPA) axis. We evaluated the effects of acute partial or total sleep deprivation on the nighttime and daytime profile of cortisol levels. Plasma cortisol profiles were determined during a 32-hour period (from 1800 hours on day 1 until 0200 hours on day 3) in normal young men submitted to three different protocols: normal sleep schedule (2300-0700 hours), partial sleep deprivation (0400-0800 hours), and total sleep deprivation. Alterations in cortisol levels could only be demonstrated in the evening following the night of sleep deprivation. After normal sleep, plasma cortisol levels over the 1800-2300-hour period were similar on days 1 and 2. After partial and total sleep deprivation, plasma cortisol levels over the 1800-2300-hour period were higher on day 2 than on day 1 (37 and 45% increases, p = 0.03 and 0.003, respectively), and the onset of the quiescent period of cortisol secretion was delayed by at least 1 hour. We conclude that even partial acute sleep loss delays the recovery of the HPA from early morning circadian stimulation and is thus likely to involve an alteration in negative glucocorticoid feedback regulation. Sleep loss could thus affect the resiliency of the stress response and may accelerate the development of metabolic and cognitive consequences of glucocorticoid excess.

Adult↗

PubMed1996

Relationships between sleep quality and glucose regulation in normal humans.

To define the effects of sleep on glucose regulation, we analyzed plasma glucose levels, insulin secretion rates (ISR), and plasma growth hormone and cortisol levels in normal subjects receiving a constant glucose infusion during nocturnal sleep, nocturnal sleep deprivation, and daytime recovery sleep. Plasma glucose and ISR markedly increased during early nocturnal sleep and returned to presleep levels during late sleep. These changes in glucose and ISR appeared to reflect the predominance of slow-wave (SW) stages in early sleep and of rapid-eye-movement and wake stages in late sleep. Major differences in glucose and ISR profiles were observed during sleep deprivation as glucose and ISR remained essentially stable during the first part of the night and then decreased significantly, despite the persistence of bed rest and constant glucose infusion. During daytime recovery sleep, SW stages were increased, glucose levels peaked earlier than during nocturnal sleep, and the decreases of glucose and ISR in late sleep were reduced by one-half. Thus sleep has important effects on brain and tissue glucose utilization, suggesting that sleep disturbances may adversely affect glucose tolerance.

Adult↗

PubMed1996

Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol.

Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.

Adult↗

PubMed1996

Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.

To assess the effects of prolonged administration of a novel analog of GH-releasing peptide (MK-677), nine healthy young men participated in a randomized, double blind, three-period cross-over comparison of orally administered placebo and 5- and 25-mg doses of MK-677. Each period involved bedtime administration of the drug for 7 consecutive days. At the end of each period, plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured at 0745 h, and 24-h profiles of plasma GH and cortisol were obtained at 15-min intervals together with the 24-h urinary excretion of free cortisol. Profiles of plasma free cortisol were calculated at hourly intervals. The amounts of GH secreted were similar in all three conditions, but GH pulse frequency was increased with both dosages of the drug, primarily because of an increase in the number of low amplitude pulses. Plasma IGF-I levels were increased in a dose-dependent manner, whereas IGFBP-3 levels were increased only with the highest dosage. There was a positive relationship between GH pulse frequency and IGF-I increase. Except for an advance in the nocturnal nadir and in the morning elevation, MK-677 had no effect on cortisol profiles. In particular, 24-h mean levels of plasma total and free cortisol and urinary excretion of free cortisol were similar under all conditions. The present data suggest that the use of MK-677 for the treatment of relative somatotropic deficiency, particularly in older adults compromised by such deficiency, deserves further investigation.

Administration, Oral↗

PubMed1996

Progressive elevation of plasma thyrotropin during adaptation to simulated jet lag: effects of treatment with bright light or zolpidem.

It is well known that TSH secretion is modulated by sleep and circadian rhythmicity, but effects of abrupt shifts of the sleep-wake and dark-light cycles such as occur in jet lag and shift work have not been investigated. The present study examines alterations in the 24-h profiles of plasma TSH and thyroid hormones following an 8-h advance shift achieved without enforcing prolonged sleep deprivation. The effects of bright light exposure or sleep facilitation with zolpidem were investigated in separate studies performed in the same subjects. Each study involved blood sampling at 20-min intervals for 68 h and included a baseline period with dim light during waking hours and 2300-0700 h bedtimes in total darkness. The 8-h shift was achieved by advancing bedtimes to 1500-2300 h. In the course of adaptation to the shift, TSH levels increased progressively in all three studies because daytime sleep failed to inhibit TSH and nighttime wakefulness was associated with large TSH elevations. The overall elevation of TSH tended to be paralleled by a small increase in T3, but not free T4, levels. In the absence of treatment, mean TSH levels following awakening from the second shifted sleep were more than 2-fold higher than during the same time interval following normal nocturnal sleep (2.10 +/- 0.22 mU/L vs. 1.04 +/- 0.14 mU/L; n = 8, P < 0.001). Bright light exposure limited the overall increase of TSH, and mean TSH levels at the end of the study were lower than in the absence of treatment (P < 0.03). Treatment with zolpidem during the first shifted night limited the overall increase in TSH levels during the following waking period (P < 0.05), but the beneficial effect was no longer significant following the second shifted night. Thus, the jet lag syndrome may be associated with a prolonged elevation of peripheral TSH levels that may be limited by treatment with bright light exposure or hypnotic facilitation of sleep.

Adaptation, Physiological↗

PubMed1995

Effects of bedtime administration of zolpidem on circadian and sleep-related hormonal profiles in normal women.

Short-acting benzodiazepine hypnotics may phase-shift circadian rhythms and improve adaptation of sleep patterns to abrupt time shifts, depending on the timing of administration. The aim of the present study was to determine whether bedtime administration of zolpidem, a non-benzodiazepine hypnotic, causes alterations in circadian rhythmicity or in the normal interactions between sleep and hormones. Eight normal women (aged 21-33 years) each participated in a baseline study and a study with zolpidem administration. On each occasion, blood samples were obtained at 20-minute intervals for 25 hours, starting at 1000 hours. Zolpidem (10 mg) was given orally at 2245 hours. Zolpidem administration was associated with an increase in stages III + IV sleep. Cortisol, melatonin, thyrotropin and growth hormone profiles were similar in both experimental conditions. In contrast, though remaining in the normal range, the nocturnal elevation of prolactin was enhanced two-fold in all subjects after zolpidem during early sleep, and prolactin levels were still 50% higher than baseline in late sleep. Morning levels were similar in both studies. In conclusion, bedtime administration of 10 mg zolpidem, a standard clinical dosage, systematically induces a transient moderate hyperprolactinemia, but does not alter other sleep-related hormonal secretions or endocrine markers of circadian rhythmicity.

Adult↗

PubMed1995

24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.

Under basal and stimulated conditions, normal insulin secretion oscillates with periods in the ultradian 100-150-min range. To test the hypothesis that oscillatory insulin delivery is more efficient in reducing blood glucose levels than continuous administration, nine normal young men were each studied on two occasions during a 28-h period including a period of polygraphically recorded sleep. Endogenous insulin secretion was suppressed by somatostatin, a constant intravenous glucose infusion was administered, and exogenous insulin was infused either at a constant rate or in a sinusoidal pattern with a period of 120 min. The mean glucose level over the 28-h period was 0.72 +/- 0.31 mmol/liter lower when insulin was infused in an oscillatory pattern than when the rate of infusion was constant (P < 0.05). The greater hypoglycemic effect of oscillatory versus constant infusion was particularly marked during the daytime, with the difference averaging 1.04 +/- 0.38 mmol/liter (P < 0.03). Serum insulin levels tended to be lower during oscillatory than constant infusion, although the same amount of exogenous insulin was administered under both conditions. Ultradian insulin oscillations appear to promote more efficient glucose utilization.

Adult↗

PubMed1994

Demonstration of rapid light-induced advances and delays of the human circadian clock using hormonal phase markers.

To determine the magnitude and direction of phase shifts of human circadian rhythms occurring within 1 day after a single exposure to bright light, plasma thyrotropin, melatonin, and cortisol levels and body temperature were monitored for 38 h in 17 men who were each studied two times, once during continuous dim light conditions and once with light exposure. After a period of entrainment to a fixed sleep-wake cycle, a 3-h light pulse (5,000 lux) was presented under constant routine conditions, and the resultant phase shifts were measured, also under constant routine conditions, on the 1st day after pulse presentation. The phase shifts in response to light occurred within 24 h and were in the delaying direction for most of the nocturnal period, with the crossover to phase advances occurring approximately 1 h after the temperature minimum. Phase shifts averaged 1 h, with delays being larger than advances, and were achieved without significant changes in rhythm amplitude. The immediate response of the human circadian clock to a single 3-h light pulse is thus characteristic of "type 1" resetting.

Adult↗

PubMed1994

Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men.

To determine whether a single episode of physical activity is capable of inducing rapid phase shifts in human circadian rhythms, 17 subjects were studied two times under constant routine conditions, once in the absence of stimulus and once with a 3-h nighttime pulse of exercise interrupting the constant routine conditions. The profiles of plasma cortisol, thyrotropin (TSH), and melatonin and of body temperature were monitored continuously to derive estimations of circadian phase position. The phase shifts were measured on the 1st day after exercise exposure. The timing of the exercise period ranged from -5 h to +4 h around the time of the minimum body temperature rhythm. Nighttime exercise was associated with 1- to 2-h phase delays of both the melatonin and TSH rhythms, with the size of the delays tending to be smaller when the exercise was presented in the latter part of the nighttime period and in the early morning. These data demonstrate that nonphotic stimuli may exert phase-shifting effects on the human circadian pacemaker.

Adult↗

PubMed1993

Preliminary studies on the immediate phase-shifting effects of light and exercise on the human circadian clock.

The aim of the present research was to determine the magnitude and direction of immediate phase shifts of human rhythms following a single exposure to a 3-hr pulse of bright light or physical activity. The pulse of light or activity was presented under "constant-routine" conditions, and measurements of the resultant phase shifts were performed under the same constant-routine conditions on the first day following pulse presentation. Four overt rhythms that are strongly dependent on circadian timing--namely, the rhythms of plasma cortisol, plasma thyroid-stimulating hormone (TSH), plasma melatonin, and body temperature--were monitored. The analysis of the TSH profiles indicated that exposure to light at about the time of the minimum of body temperature resulted in phase advances averaging less than 1 hr in magnitude. Exposure to light approximately 3 hr before the time of the minimum of body temperature resulted in phase delays of 1-2 hr. Preliminary analyses of the melatonin profiles have confirmed these observations. Our findings regarding the effects of exercise are still inconclusive.

Adult↗