Biomedical subjects

W Kern

Publications and source records attributed to W Kern.

At least 109 records · Page 6Linked to original sources

PubMed1996

Changes in cortisol and growth hormone secretion during nocturnal sleep in the course of aging.

BACKGROUND: One current hypothesis of biological aging proposes that aging results from the deterioration of neuroendocrine functions. Sleep dependent growth hormone (GH) secretion is diminished in elderly people. However, the time course of this decrease from puberty to senescence is still unknown. Cortisol secretion is also related to sleep processes with the 24 hr nadir occurring, like the sleep dependent GH secretory surge, during the first half of nocturnal sleep. Whether age also affects the sleep-associated nadir of cortisol secretion has yet to be clarified. This study investigated changes in GH and cortisol secretion during sleep in 30 male volunteers age 20 to 92 yr. METHODS: After an adaptation night, each subject spent another night in the sleep laboratory for polygraphic sleep recording and determination of GH and cortisol levels every 15 min. RESULTS: GH peak values exponentially decreased with age (r = -.80, p < .001), while the cortisol nadir increased linearly as a function of age (r = .79, p < .001). Age-related changes in sleep-dependent secretion of GH and cortisol correlated significantly (r = .47, r = -.55, respectively; p < .05) with an age-dependent decrease in slow wave sleep. CONCLUSION: Alterations of GH peak amplitude and basal cortisol secretion are not restricted to senescence. These changes develop gradually during adult life with different time courses. Both changes in GH and cortisol secretion may act together to reduce anabolic functions of sleep in the aged.

Adult↗

PubMed1996

Optimizing therapy for acute myeloid leukemia based on differences in intracellular metabolism of cytosine arabinoside between leukemic blasts and normal mononuclear blood cells.

The increasing insights into the pharmacokinetics and the metabolism of arabinoside C (AraC) have improved the rationale for its application in leukemia therapy and have led to a pharmacologically directed design of antileukemic treatment. The current study aims at adding to this approach by detecting differences in the intracellular metabolism of AraC 5'-triphosphate (AraCTP) between leukemic and normal mononuclear blood cells. Measurements of intracellular AraCTP levels were complemented by determinations of plasma AraC and arabinoside uridine (AraU) concentrations and were performed in 26 patients with acute myeloid leukemia (AML) who were undergoing combination therapy, including high-dose (1.0 or 3.0 g/m2 x 2/day) AraC. Plasma AraC concentrations showed a linear relationship to the applied AraC dose but did not correlate with intracellular AraCTP levels. Substantial differences in AraCTP retention times were revealed, during 3-h infusions of either 1.0 or 3.0 g/m2 AraC in leukemic blasts from 10 patients with t1/2 values of 1.60-7.63 h (median, 2.42 h). In addition, AraCTP levels declined in only one patient by > 10% within the first hour after the end of therapy and remained constant or even increased up to 1.5-fold during a posttreatment period of 1-2.5 h in the other nine cases. In contrast, AraCTP retention times were relatively uniform in normal mononuclear blood cells from 11 patients, with t1/2 values of 3.34-5.29 h (median, 3.85 h). More importantly, AraCTP levels dropped by > 10% within the first hour after the end of the high-dose AraC infusion in eight of 11 cases. A posttherapeutic increase of > 10% was not observed in any patient. These differences in AraCTP pharmacokinetics between leukemic and normal blood cells provided the basis for a modified timing of AraC administration with the aim of selectively maintaining cytotoxic AraCTP levels in leukemic blasts while allowing an intermittent drop of AraCTP levels in normal cells. This modification may result in higher antileukemic activity without increasing the damaging effect on normal cells and may, thus, improve the therapeutic index for AraC.

Acute Disease↗

PubMed1996

Entrainment of ultradian oscillations in the secretion of insulin and glucagon to the nonrapid eye movement/rapid eye movement sleep rhythm in humans.

The cause of ultradian oscillations in the secretion of glucagon and insulin with a period length between 70-140 min has been atttributed to feedback mechanisms of glucose and insulin. Influences of the central nervous system on these ultradian glucagon and insulin oscillations remained to be elucidated. In the present study on one occasion, concentrations of glucose, glucagon, insulin, and GH were determined at 15-min intervals from 2100-0700 h in 16 healthy subjects while they were infused with saline solution. On another occasion, concentrations of these hormones during nocturnal sleep were determined in 10 of these subjects while they were constantly infused with glucose (4.5 mg/kg x min). The order of the treatments (placebo vs. glucose) was balanced across subjects, and experiments were performed in a double blind manner. Significant glucagon and insulin peaks were determined by the peak detection algorithm Cluster. Sleep was recorded somnopolygraphically. During the infusion of saline solution, glucagon concentrations showed spontaneous oscillations, with a mean periodicity of 107.9 +/- 13.2 min. During the constant infusion of glucose, oscillations of similar periodicity (110.1 +/- 10.3 min) were observed for insulin. The phases of glucagon and insulin secretory activity on the respective nights were entrained to the nonrapid eye movement (non-REM)/REM sleep cycle. Significant increases in the concentrations of glucagon (chi 5.23; P < 0.02) and insulin (chi= 7.32; P < 0.01) generally fell into epochs of non-REM sleep, with a preference for the beginning of the epochs, whereas decreasing concentrations of these hormones coincided significantly with epochs of REM sleep (P < 0.05). The time spent in the different sleep stages was not altered during glucose infusion. In conclusion, ultradian oscillations of insulin and glucagon concentrations are modulated by central nervous system mechanisms entraining secretory pulses of the alpha- and beta-cells of the endocrine pancreas to the non-REM sleep epochs of the non-REM/REM sleep cycle.

Activity Cycles↗

PubMed1996

Oral idarubicin pharmacokinetics--correlation of trough level with idarubicin area under curve.

Idarubicin is the first anthracycline that can be successfully administered via the oral route and thus may facilitate antineoplastic chemotherapy at an improved quality of life. These perspectives are somewhat hampered by the large variation in bioavailability between individual patients and the obvious requirement to monitor plasma concentration and area-under the curve values (AUC) for an appropriate adjustment of idarubicin dose. In this study we describe the pharmacokinetics of idarubicin and its main metabolite idarubicin in 12 patients after oral application of 20 mg/m2 idarubicin on 3 consecutive days and demonstrate that the 24-h trough levels shows high correlation with AUC and may thus allow a rapid and easy determination of individual drug concentrations and an appropriate dose adjustment. The average terminal half-life was 30.5h for idarubicin and 66.9 h for idarubicinol. The AUC for idarubicin and its main metabolite idarubicinol revealed a substantial interpatient variation with AUC values ranging from 25.7 to 114 ng x h/ml (average 58.1 ng x h/ml) for idarubicin and from 109.4 - 445.2 ng x h/ml (average 287.3 ng x h/ml) for idarubicinol. However, the ratio of idarubicin/idarubicinol differed only two-fold from 1:3.7 to 1:7.7 with an average of 1:5.1. Both idarubicin and idarubicinol concentrations were highly reproducible, however, upon measurements after repeated applications within individual patients. Moreover, idarubicinol and idarubicin AUCs showed a good correlation with r=0.78, indicating that the interindividual variations of idarubicin AUC reflects differences in absorptions rather than metabolism. In order to describe the interindividual bioavailability of idarubicin - represented by AUC - measurement of a single data point with a high correlation with the AUC would be ideal. Our study demonstrates that the 24-h trough level shows such an excellent correlation (r=0.96) with AUC, making it the perfect candidate for fast estimates of the individual bioavailability in a given patient. On this basis, the longitudinal measurement of the 24-h trough level may allow the assessment of the impact of interindividual variations in AUC of clinical outcome and toxicity.

Acute Disease↗

PubMed1995

Gas chromatographic-electron impact mass spectrometric screening procedure for unknown hydroxyaldehydic lipid peroxidation products after pentafluorobenzyloxime derivatization.

Aldehydic lipid peroxidation products can be detected after transformation to pentafluorobenzyloxime derivatives by GC-MS screening using characteristic ion traces. Thus the rather unstable unsaturated hydroxyaldehyde, 6-hydroxy-2,4-undecadienal, was identified as autoxidation product of linoleic acid. Its structure was unambiguously confirmed by comparison with an authentic sample. After Fe(2+)-ascorbate induced lipid peroxidation of oleic acid several 4-hydroxy-2-alkenals and 4-hydroxyalkanals were detected. These represent previously unknown secondary oxidation products of lipid peroxidation of oleic acid. Nevertheless oleic acid proved about 1000 times more stable against peroxidation than linoleic or higher unsaturated acids.

Aldehydes↗

PubMed1995

Hormonal secretion during nighttime sleep indicating stress of daytime exercise.

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800-2030), and 3) LDE of moderate intensity (biking 120-150 km; 1600-2030). During the subsequent night (2300-0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.

Adult↗

PubMed1995

Nocturnal wakefulness inhibits growth hormone (GH)-releasing hormone-induced GH secretion.

Recent studies have suggested that spontaneous release of GH as well as GH secretion stimulated by exogenous GHRH are influenced by central nervous mechanisms that regulate sleep and wakefulness. Here, the effect of nocturnal wakefulness on GH secretion stimulated by i.v. administration of GHRH was examined in two experiments in healthy men. On all nights, GHRH (1 microgram/kg BW) was injected after the subjects had slept for about 2.5 h to minimize interference of endogenous release of GH during early sleep with the response to exogenous GHRH. Both experiments included a control condition to assess GH secretory responses to GHRH during undisturbed sleep and an experimental condition to assess the effect of wakefulness. In the control conditions, subjects slept throughout the night, and GHRH was administered 170 min after sleep onset. In the experimental condition of Exp I (n = 10), subjects were awakened 150 min after sleep onset and stayed awake. GHRH was given 20 min after awakening. In the experimental condition of Exp II (n = 8), subjects were awakened 30 min after GHRH treatment, which was administered 170 min after sleep onset. GHRH administrations during sleep fell into epochs of stage 2 sleep or rapid eye movement sleep. GH secretion and sleep characteristics before GHRH administrations were comparable for experimental and control conditions of both experiments. GH secretory responses were inhibited when the subject was awake at the time of GHRH administration compared to GH responses during undisturbed sleep. Awakening the subject 30 min after GHRH administration abruptly interrupted the initiated GH secretory response. The results demonstrate a profound inhibitory effect of nocturnal awakenings on GHRH-induced GH secretion. They indicate that the GH secretory response to GHRH is strongly determined by central nervous system sleep-wake activity.

Adult↗

PubMed1994

Polyclonal antibodies directed against an epitope specific for the alpha 4-subunit of GABAA receptors identify a 67-kDa protein in rat brain membranes.

Polyclonal antibodies were raised to the C-terminal part of the gamma-aminobutyric acidA (GABAA) receptor alpha 4-subunit. These anti-peptide alpha 4 (517-523) antibodies specifically identified a protein with apparent molecular mass 67 kDa in rat brain membranes. This protein was enriched by immunoaffinity chromatography of brain membrane extracts on Affigel 10 coupled to the anti-peptide alpha 4 (517-523) antibodies and could then be identified by the anti-alpha 4-antibodies as well as by the GABAA receptor subunit-specific monoclonal antibody bd-28. This appears to indicate that the 67-kDa protein is the alpha 4-subunit of GABAA receptors. Intact GABAA receptors appeared to be retained by the immunoaffinity column because other GABAA receptor subunit proteins like the beta 2/beta 3-subunits and the gamma 2-subunit were detected in the immunoaffinity column eluate. Furthermore, in addition to the 67-kDa protein, a 51-kDa protein could be detected by the antibody bd-28 and the anti-peptide alpha 4 (517-523) antibody in the immunoaffinity column eluate. A protein with similar apparent molecular mass was identified by the alpha 1-subunit-specific anti-peptide alpha 1 (1-9) antibody. In contrast to the alpha 1-subunit, the 51-kDa protein identified by the anti-alpha 4 antibody could not be deglycosylated by N-Glycanase. The identity of the 51-kDa protein identified by the anti-alpha 4-antibodies thus must be further investigated.

Animals↗

PubMed1994

Effects of insulin and hypoglycemia on the auditory brain stem response in humans.

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.

Adolescent↗

PubMed1994

Effects of diurnal sleep on secretion of cortisol, luteinizing hormone, and growth hormone in man.

Evidence has been provided for an influence of nocturnal sleep on the secretion of cortisol, LH, and GH in man. Although nocturnal sleep inhibits cortisol secretion during the first hours, it augments the secretion of LH and GH. To separate the effects of circadian rhythm from those of sleep, the present experiments examined the influence of diurnal sleep on the release of cortisol, LH, and GH in 12 young men. Subjects slept on 2 different occasions. After a night of wakefulness, subjects were assigned to bed at 0800 h the following morning. Lights were turned off either at 1100 or 1500 h to enable sleep. Effects of diurnal sleep were evaluated by comparing blood hormone concentrations during the interval from 1100-1500 h between subjects when sleeping and awake. Comparing hormonal concentrations during the 4 h of sleep after 1100 h with those during the 4-h sleep interval after 1500 h provided evidence for an influence of circadian rhythm on cortisol and LH release. Diurnal sleep, as has been shown for nocturnal sleep, augmented the secretion of LH and GH. However, in contrast to nocturnal sleep, diurnal sleep failed to suppress cortisol release, suggesting that sleep does not inhibit cortisol release at any point of its circadian rhythm, but only within a limited range of entrainment.

Adult↗

PubMed1994

Evidence for effects of insulin on sensory processing in humans.

Systemic insulin passes the blood-brain barrier and insulin receptors have been detected in various brain regions. Yet, the biological significance of insulin acting on the brain remains rather unclear. Reports of different awareness of hypoglycemic symptoms during hypoglycemia induced by human insulin (HI) and porcine insulin (PI) suggest a modulatory influence of insulin on sensory processing. In a double-blind, within-subject, crossover comparison, we recorded visual-evoked potentials (VEP) in 30 healthy men during euglycemia and after 20 or 50 min of constant hypoglycemia of 2.66 mM (47.9 mg/dl) induced by HI and PI. Blood glucose and serum insulin levels were identical in both sessions. Hypoglycemia reduced amplitudes of the VEP components P1 and N2 and increased latencies of N1, P1, and N2. However, hypoglycemia-induced changes in VEP amplitudes and latencies were significantly stronger during PI and HI infusion: P1-N2 difference amplitude decreased from (mean +/- SE) 11.9 +/- 0.9 to 10.7 +/- 0.8 muV during HI and from 12.4 +/- 0.9 to 8.7 +/- 0.7 muV during PI infusion (P < 0.002). P1 latency increased from 112.0 +/- 3.2 to 118.8 +/- 3.2 ms during HI and from 114.0 +/- 3.3 to 126.3 +/- 4.6 ms during PI infusion (P < 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, which indicates a short-term action of the hormone. The results add to those of a foregoing study demonstrating differential effects of HI- and PI-induced hypoglycemia on auditory evoked potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Cadmium and lead in the smoke of a filter cigarette.

Cadmium and lead were determined in the parts of a filter cigarette after fractional smoking. The partitioning of these elements into the main smoke stream, consisting of particulates and gases, also into the side stream, the ash and the butt was determined. Approximately 70% of the lead mobilized by the smoking process was found in the ash; about 50% of the cadmium was transferred into the side stream. The overall trend shows an increase in the amount of the metals in the main stream as the number of puffs is increased. A model for the behavior of the main stream components within the cigarette was developed and showed a high analogy with the Lambert-Beer law describing the absorption of light.

Cadmium↗

PubMed1993

Classically conditioned changes of blood glucose level in humans.

Procedures of classical conditioning in animals and man have provided evidence that most psychophysiological responses can be acquired by repeated association with previous neutral stimuli. Many animal studies reported on conditioned changes in the blood glucose level; the nature of the conditioned response (CR), hypo- or hyperglycemia, however, seems to vary with experimental procedures. The present study aimed to elicit conditioned blood glucose changes in human subjects. Thirty male volunteers participated in five sessions each. The sessions were separated by 3 days, with identical time course and procedure. The subjects were informed that we wanted to test the effects of insulin or placebo injections on cognitive functioning, and were kept busy with pseudotests. In four sessions, subjects were injected with 0.035 IU/kg body weight of human insulin as the unconditioned stimulus (US), which induced the expected fall in blood glucose level below 50 mg/dl (UR). Injections were accompanied by a specific stimulus compound (conditioned stimulus, CS) in half of the subjects. In the fifth session, the CS was associated with a placebo injection. About half of the subjects showed a change from the baseline level of blood glucose of more than 10 mg/dl, which we would interpret as a conditioned response. Conditioning occurred more often in those subjects who were given a CS compound in addition to the injection, which itself together with the experimental environment may have been a sufficient CS.

Adult↗

PubMed1993

Auditory reflex thresholds elevated by stress-induced cortisol secretion.

To study steroid effects on auditory perception, 24 volunteers were unexpectedly confronted with a psychological stressor. Auditory reflexes to pure tones and noise were recorded before stress exposure, up to 100 min afterwards and in a second control session. Repeated measurements of cortisol and testosterone in saliva, as well as blood pressure, heart rate, and subjective feelings confirmed the stressful nature of the test. Following stress induction the auditory reflex of the contralateral ear needed significantly higher loudness (i.e. more decibels) to be elicited than at baseline or control measures. Two lines of evidence suggest that this stress-induced change may be specifically related to glucocorticoid actions: (1) In a previous study similar elevations in auditory reflex threshold had been obtained by the administration of exogenous glucocorticoids (hydrocortisone), and (2) in the present study the overall effect of stress induction on acoustic reflex described above was mainly observed in a subgroup of subjects, who responded to the stressor with a marked rise in free cortisol.

Acoustic Stimulation↗

PubMed1993

Entrainment of nocturnal pituitary-adrenocortical activity to sleep processes in man--a hypothesis.

The 24 hr patterns of plasma ACTH and cortisol concentrations are characterized by prominent circadian and ultradian oscillations. Usually both, nadir and acrophase of the circadian rhythm occur during sleep. This led us to re-evaluated the temporal relationship between sleep processes and nocturnal plasma ACTH and cortisol levels and the impact of several types of sleep manipulation (sleep delay, sleep disruption, sleep prolongation, sleep deprivation, and reversal of the sleep-wake cycle). Pituitary-adrenocortical activity appeared to be linked to the cyclic process of nocturnal sleep with inhibitory influences present during the first two sleep cycles. After initiation of the third sleep cycle stimulatory effects of sleep prevailed, lasting until awakening. The sleep associated influences appeared to act in concert with influences of circadian oscillators and resulted in an amplification of the circadian rhythm of pituitary-adrenal activity; they were strong enough to entrain the circadian rhythm of the pituitary-adrenal system to the sleep-wake cycle, as long as phase delays were moderate. However, with acute sleep-wake reversals the sleep associated influences were masked by the dominant effects of the circadian clock. In contrast, GH secretion appeared to be controlled primarily be sleep-associated mechanism with only minor circadian influences.

Adrenal Cortex↗

PubMed1993

Antimineralocorticoid canrenoate enhances secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis in humans.

In rats, both hippocampal glucocorticoid and mineralocorticoid receptors (MR) have been shown to participate in the regulation of basal hypothalamus-pituitary-adrenocortical (HPA) secretory activity. Inhibition of hippocampal MRs enhanced the activity of the HPA axis in these animals. We tested the influence of potassium cancrenoate, a selective MR antagonist, on basal cortisol secretion in 10 healthy young men during sleep. Cortisol, ACTH, vasopressin and growth hormone (GH) were determined at 22.00, 23.00, 01.00, 04.00 and 07.00 h. Sleep was monitored by somnopolygraphy. Potassium canrenoate (200 mg) was administered intravenously at 08.00 and 17.00 h the preceding day. Compared with a placebo condition, potassium canrenoate elevated cortisol levels throughout the night, with significant (p < 0.05) increases at 22.00, 23.00, 01.00 and 07.00 h. Effects of canrenoate on ACTH levels were not significant, and there was also no effect on plasma vasopressin levels. GH concentrations at 04.00 and 07.00 h were higher after canrenoate than placebo (p < 0.05). Changes induced by canrenoate paralleling those in animals after intracerebroventricular administration of MR antagonists suggest that central nervous MRs are involved in the regulation of HPA secretory activity also in humans.

Adult↗

PubMed1993

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women.

Whereas the nocturnal slowing of the LH pulse frequencies in the early follicular phase (EFP) of the menstrual cycle may be attributed to a sleep-associated increase in opioidergic activity, the concomitant augmentation of LH pulse amplitudes remains unexplained. We reasoned whether alterations in the pituitary gonadotropin responsiveness during the 24-hour rest-activity cycle may account for these enhanced LH pulse amplitudes during sleep. Accordingly, 12 EFP women (cycle days 3-5) were studied on 2 consecutive days during three occasions: a day time between 1000 and 1400 h (day studies), at night between 2200 and 0200 h, while the women were awake (night studies), and finally, during identical night hours, while the women were asleep (sleep studies). At all occasions, blood was collected at 10-min intervals for 4 h, while GnRH (25 micrograms) was administered twice within 2 h. During the day studies, prompt and sustained LH and FSH releases were noted in response to the first and second GnRH stimulations. However, the LH and FSH release after both the first and second GnRH challenges was markedly (P < 0.01) blunted during the night studies. By contrast, this decrease in LH, but not FSH response during the night was completely prevented, when GnRH was administered during sleep. Independent of the time at which GnRH had been administered, the second GnRH stimulations provoked much greater (P < 0.05 or less) LH and FSH releases than the first. Thus, a marked attenuation of the gonadotroph responsiveness is observed in EFP women during the night, and nocturnal sleep may eliminate this decline. Further, the priming actions on the gonadotrophs by repetitive GnRH stimulations are unaffected by the time of GnRH administrations. Collectively, these observations permit us to infer that the increased LH pulse amplitudes observed during sleep in EFP women may not be attributed to increased pituitary responsiveness.

Adult↗

PubMed1993

Systemic growth hormone does not affect human sleep.

Subsequent to sleep onset, GH concentrations increase markedly, suggesting a stimulatory influence of sleep on GH secretion. However, results have been inconsistent as to whether GH conversely exerts a significant influence on sleep. Hence, the effects of exogenous administration of GH and of GH secretion stimulated by GH-releasing hormone (GHRH) on sleep were reexamined in 3 experiments in healthy male volunteers. In Exp I, 12 men participated on 3 experimental nights, receiving a constant iv infusion of 5 IU GH (between 2100-0700 h), an im bolus injection of 5 IU GH at 2100 h, and placebo. In Exp II, the effects of a short iv infusion of a high dose of 48 IU GH (between 2345-2315 h) on sleep were evaluated in 3 men. In Exp III, the effects of continuous infusion of 30 micrograms/h GHRH (between 2200-0700 h) on sleep were compared to the placebo condition in 10 men. Experiments were double blind, within-subject, cross-over comparisons and included an adaptation night before experimental nights. On all nights, the subjects went to bed at 2300 h and were awakened at 0700 h. Administration of GH elevated plasma GH and somatomedin-C levels throughout the night (P < 0.005). Neither im administration of 5 IU GH nor iv administration of 5 and 48 IU GH had any effect on the total sleep time or the time spent in different sleep stages during the whole night or in the first and second halves of sleep time. Infusion of GHRH increased nocturnal GH secretion (P < 0.005), but the episodic pattern of GH secretion was maintained. However, sleep remained unchanged during GHRH infusion. From these results we conclude that in healthy man, systemic GH has no physiological role for sleep regulation.

Adult↗