Biomedical subjects

A Steiger

Publications and source records attributed to A Steiger.

At least 55 records · Page 3Linked to original sources

PubMed1998

Effects of hormones on sleep.

Administration of hormones to humans and animals results in specific effects on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. Studies with pulsatile administration of various neuropeptides in young and old normal controls and in patients with depression suggest they play a key role in sleep-endocrine regulation. Growth hormone (GH)-releasing hormone (GHRH) stimulates GH and slow wave sleep (SWS) and inhibits cortisol, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. Changes in the GHRH:CRH ratio contribute to sleep-endocrine aberrations during normal ageing and acute depression. In addition, galanin and neuropeptide Y promote sleep, whereas, in the elderly, somatostatin impairs sleep. The rapid eye movement (REM)-nonREM cycle is modulated by vasoactive intestinal polypeptide. Cortisol stimulates SWS and GH, probably by feedback inhibition of CRH. Neuroactive steroids exert specific effects on the sleep EEG, which can be explained by gamma-aminobutyric acid(A) receptor modulation.

Animals↗

PubMed1998

Effects of thyrotropin-releasing hormone on the sleep EEG and nocturnal hormone secretion in male volunteers.

Various peptides including corticotropin-releasing hormone (CRH) exert selective effects on sleep structure and noctural secretions of cortisol and growth hormone (GH). In animal studies analeptic effects and sleep disturbances after thyrotropin-releasing hormone (TRH) administration have been observed; studies of endocrine function in depressed patients suggest a pathological activity of CRH and TRH as compared with that in healthy volunteers. As the role of TRH in the regulation of the sleep endocrine pattern in humans has not yet been clarified, we performed a study to examine the effects of pulsatile administration of TRH on the sleep EEG pattern and the nocturnal secretions of cortisol and GH in 7 healthy male subjects. The sleep EEG was recorded from 23.00 to 07.00 h, and blood samples were collected every 20 min from 20.00 to 07.00 h for the analysis of GH and cortisol concentrations during intravenous administration of placebo or 4 x 50 microgram TRH at 22.00, 23.00, 24. 00, and 01.00 h. In contrast to the well-known effects of CRH on the sleep endocrine pattern, TRH exerts only a weak effect on the sleep EEG which is reflected in a slight decrease in sleep efficiency associated with a trend to wakefulness during the night. Furthermore, after TRH administration, the cortisol rise appeared earlier, and a nonsignificant tendency to an increased secretion of cortisol during the first half of the night was found. The GH secretion did not differ significantly after application of TRH or placebo. The activating, albeit weak, effect of TRH on the sleep EEG and nocturnal cortisol secretion in healthy volunteers confirms and adds to the results previously observed in animals. On the basis of these findings, we surmise that TRH may contribute to the disturbed sleep continuity seen in depressed patients, probably acting as a cofactor of CRH in a synergistic manner.

Adult↗

PubMed1998

Enhanced slow wave sleep in patients with prolactinoma.

Bidirectional interactions between nocturnal hormone secretion and sleep regulation are well established. In particular, a link between PRL and rapid eye movement (REM) sleep has been hypothesized. Short-term administration of PRL and even long-term hyperprolactinemia in animals increases REM sleep. Furthermore, sleep disorders are frequent symptoms in patients with endocrine diseases. We compared the sleep electroencephalogram of seven drug-free patients with prolactinoma (mean PRL levels 1450 +/- 1810 ng/mL; range between 146 and 5106 ng/mL) with that of matched controls. The patients had secondary hypogonadism but no other endocrine abnormalities. They spent more time in slow wave sleep than the controls (79.4 +/- 54.4 min in patients vs. 36.6 +/- 23.5 min in controls, P < 0.05). REM sleep variables did not differ between the samples. Our data suggest that chronic excessive enhancement of PRL levels exerts influences on the sleep electroencephalogram in humans. Our result, which seems to be in contrast to the enhanced REM sleep under hyperprolactinemia in rats, leads to the hypothesis that both slow wave sleep and REM sleep can be stimulated by PRL. These findings are in accordance with reports of good sleep quality in patients with prolactinoma, which is in contrast to that of patients with other endocrine diseases.

Adult↗

PubMed1998

[The evaluation of breed-specific defects in dog breeds from an animal welfare viewpoint].

Issues of breed defects such as morphology, physiology or behaviour in pure-breed dogs, are briefly discussed. Suggestions for various kinds of improvements are made, particularly concerning legislation, analysis of pedigree to avoid undesirable breed characteristics and what breeding clubs, individual breeders, judges, future dog owners and veterinarians could and should do about these problems; these are followed by summary conclusions.

Animal Welfare↗

PubMed1997

Nocturnal secretion of prolactin and cortisol and the sleep EEG in patients with major endogenous depression during an acute episode and after full remission.

We investigated the sleep electroencephalogram (EEG) and the nocturnal secretion of prolactin and cortisol in 25 normal subjects and 12 male inpatients with major depression before treatment and after remission and drug withdrawal. In the depressed patients, sleep-EEG disturbances persisted after recovery, whereas the cortisol concentration decreased. Prolactin variables in the patients did not differ between the two time points (i.e. before treatment and after remission). Compared with the normal subjects, the patients had significantly higher cortisol concentrations. The above findings were not altered when age was used as a covariate in statistical analysis. Our data suggest that neither depression nor aging exerts distinct effects on prolactin secretion.

Adult↗

PubMed1997

The GABAA agonist THIP produces slow wave sleep and reduces spindling activity in NREM sleep in humans.

Recent studies in the rat demonstrated that systemic administration of muscimol and THIP, both selective GABAA receptor agonists, elevates slow wave activity in the EEG during non-rapid eye movement (NREM) sleep. In this placebo-controlled study, we assessed the influence of an oral dose of 20 mg THIP on nocturnal sleep in young healthy humans. Compared to placebo, THIP increased slow wave sleep by about 25 min. Spectral analysis of the EEG within NREM sleep revealed significant elevations in the lower frequencies (< 8 Hz) and reductions in the spindle frequency range (approximately 10-16 Hz). In accordance with previous findings in the rat, these data imply that GABAA agonists promote deep NREM sleep, without suppressing REM sleep. These effects are opposite to those induced by agonistic modulators of GABAA receptors such as benzodiazepines and are at variance with established mechanisms according to which GABAA agonists and modulatory agonists would have similar effects. The sleep response to GABAA agonists is highly similar to that evoked by sustained wakefulness, suggesting that GABAA receptors may be implicated in the homeostatic regulation of sleep.

Adult↗

PubMed1997

Open clinical trial on the sigma ligand panamesine in patients with schizophrenia.

The sigma (sigma) receptor has been proposed as a target of neuroleptic drugs. Preclinical data suggest that panamesine (EMD 57445), a novel sigma ligand, has antipsychotic effects and is free of side effects related to the extrapyramidal motoric system (EPMS). Here we report the results of an exploratory study aimed at determining the appropriate dose range and the safety of panamesine in patients with an acute episode of schizophrenia. The first trial with four patients revealed insufficient clinical efficacy of a protocol where the daily dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks 3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning, this being increased up to 60 mg/day within 3 days and then maintained at this level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating Scale score by at least 50%, five patients were judged as responders, whereas six patients showed only a slight improvement, and one deteriorated. Moreover, intent-to-treat analysis showed significant improvement in psychometric variables. In all patients prolactin levels increased during treatment, probably due to an active metabolite with weak dopamine-2-receptor antagonistic effects. No major side effects occurred, and in particular, no EPMS symptoms were seen.

Acute Disease↗

PubMed1997

Somatostatin impairs sleep in elderly human subjects.

With increasing age, sleep becomes more shallow and fragmented and sleep-associated growth hormone (GH) release declines. GH secretion is regulated physiologically by opposite actions of GH-releasing hormone (GHRH) and somatostatin (SRIF). The administration of GHRH promotes sleep in both young and elderly controls, whereas SRIF does not induce sleep-EEG changes in young subjects. Because the influence of peripheral SRIF administration on sleep EEG in the elderly is unknown, we administered 50 micrograms SRIF-14 every hour between 2200 and 0100 hours to controls with an age range from 60 to 73 years (mean +/- SD 67.4 +/- 5.1 years). After SRIF administration, total sleep time and rapid eye movement (REM) sleep decreased significantly, and more time was spent awake in the first sleep cycle, suggesting that SRIF induces sleep deterioration in the elderly. The peptide may become more effective on sleep EEG in older than in younger subjects, because of the decline of GHRH-GH axis activity, which may contribute to sleep disturbances in aging. The increased efficacy of SRIF in the elderly also may be explained by enhanced leakage of the blood-brain barrier.

Aged↗

PubMed1997

Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration.

When administered intravenously (i.v.) in a pulsatile mode during the first half of the night to young normal controls, growth hormone-releasing hormone (GHRH) results in increased growth hormone (GH) plasma levels and slow wave sleep (SWS) and blunted cortisol release. In the present study we investigated whether GHRH has the same effects when administered in the early morning. Seven normal young male volunteers had 2 sessions each in the sleep laboratory (23.00 to 10.00 h) during which the secretion of GH, cortisol and corticotropin (ACTH) and polygraphic recording were monitored. Verum (4 bolus injections of 50 micrograms GHRH) or placebo were injected i.v. at 04.00, 05.00, 06.00 and 07.00 h. GHRH stimulated GH plasma levels significantly whereas cortisol and ACTH were not altered. In the sleep-electroencephalogram, only rapid-eye-movement density was decreased significantly during the period of active medication; all other sleep parameters were unaffected. We suggest that the physiological occurring high activity of the hypothalamic-pituitary-adrenocortical(HPA) system in the early morning prevents the effects of GHRH on cortisol plasma levels and SWS. Thus GHRH administered to healthy young men in the early morning hours has the same effect as GHRH administered during the first half of the night to patients with major depression who have HPA hyperactivity throughout the day.

Adrenocorticotropic Hormone↗

PubMed1997

Longtime administration of growth hormone-releasing hormone (GHRH) does not restore the reduced efficiency of GHRH on sleep endocrine activity in 2 old-aged subjects--a preliminary study.

Aging results in a more shallow sleep accompanied by a blunted growth hormone (GH) secretion. In young male normal controls repetitive administration of GH-releasing hormone (GHRH) at the beginning of the night results in an increased secretion of GH, a blunting of cortisol and a stimulation of slow-wave sleep (SWS). In healthy elderly men and women, however, GHRH exerts only weak effects on sleep-endocrine activity. In a previous report continuous treatment of healthy elderly males by repetitive administration of GHRH (during 12 days administration with 100 micrograms GHRH i.v. at 9.00 h every second day, "priming") enhanced GHRH stimulated GH secretion at daytime markedly. We tested if priming with GHRH results in a more distinct modulation of the nocturnal hormone secretion and of the sleep EEG than acute administration of the peptide. Two elderly male controls spent first three consecutive nights in the sleep laboratory, the first of which served for adaptation to laboratory conditions. During the two other nights (at days 1 and 2) sleep EEG was recorded and blood was sampled for determining the secretion of GH, cortisol and ACTH. In one of the nights the subjects received 50 micrograms GHRH hourly between 22.00 h and 1.00 h (4 x 50 micrograms) or placebo. The next examination followed after the priming period at day 14 and the last was performed two weeks after treatment at day 28. After the baseline administration of 4 x 50 micrograms GHRH before priming no clear changes of sleep EEG towards improved sleep were detectable, whereas GH secretion was increased. After priming sleep period time and SWS time were lower compared to the baseline night with GHRH administration, whereas REM time duration increased. GHRH induced GH secretion was not enhanced after priming. ACTH secretion was markedly enhanced compared to baseline stimulation. We conclude that priming with GHRH has no sleep improving effect and does not change hormone secretion in elderly normal subjects. Hence in the elderly priming with GHRH is not capable to induce a rejuvenation of sleep endocrine activity.

Adrenocorticotropic Hormone↗

PubMed1997

Corticotropin-releasing hormone inhibits melatonin secretion in healthy volunteers--a potential link to low-melatonin syndrome in depression?

Interactions between the hypothalamic-pituitary-adrenocortical (HPA) system and melatonin secretion have been demonstrated, but only the effects of melatonin on the activity of the HPA system have been studied in man. Alterations of melatonin secretion described as low-melatonin syndrome have been demonstrated in patients suffering from a major depressive episode, and an inhibitory factor on melatonin secretion has been postulated. We investigated whether corticotropin-releasing hormone (CRH), which is thought to be involved in HPA abnormalities in depressed patients, can also suppress melatonin secretion in healthy volunteers. Ten healthy male human volunteers in a double-blind study design received randomized hourly intravenous injections from 08.00 to 18.00 h that contained 10 micrograms human CRH, 1 microgram adrenocorticotropic hormone (ACTH), or placebo to simulate pulsatile hormone secretion. Plasma melatonin and cortisol responses during the treatment and nocturnal sleep electroencephalograms after the treatment were recorded. Administration of CRH reduced melatonin secretion significantly below values obtained after administration of placebo and ACTH. Cortisol secretion was significantly enhanced by ACTH in comparison to both placebo and CRH. Electroencephalographic sleep parameters revealed no treatment effects. Our findings suggest that CRH has an inhibitory effect on the pineal secretion of melatonin in normal man. A mechanism via a release of cortisol was not supported by our results. Secondary hormonal effects from changes in nocturnal sleep architecture were excluded. Further investigation of the action of CRH on melatonin secretion as well as the mutual feedback between the HPA system and the pineal gland may extend our knowledge of neuroendocrine alterations mediating the adaptive response to stress and the eventual involvement in the pathogenesis of depression.

Adult↗

PubMed1997

Neuropeptides and human sleep.

Results from preclinical studies have validated the participation of neuropeptides in sleep regulation. In recent human and clinical studies it has been shown that peripheral administration of various peptides results in specific changes in the sleep electroencephalogram in humans. Furthermore, it has been demonstrated that certain peptides are common regulators of the electrophysiological and neuroendocrine components of sleep. It is now well established that the balance between the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in normal and pathological sleep regulation. In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect. During normal aging and during acute depression, the GHRH:CRH ratio is changed in favor of CRH, resulting in disturbances in sleep endocrine activity. In addition to GHRH, galanin, growth hormone-releasing peptide, and neuropeptide Y also promote sleep, unlike ACTH(4-9), which disturbs sleep. In elderly subjects, sleep deteriorates after acute administration of somatostatin but improves after chronic treatment with vasopressin. Vasoactive intestinal polypeptide decelerates the non-rapid eye movement-rapid eye movement cycle and advances the occurrence of the cortisol nadir. The impact of delta sleep-inducing peptide, cholecystokinin, and thyrotropin-releasing hormone on human sleep regulation is not yet clear. This paper reviews recent work investigating the influence of these various neuropeptides on sleep.

Aging↗

PubMed1996

Trimipramine and imipramine exert different effects on the sleep EEG and on nocturnal hormone secretion during treatment of major depression.

In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.

Adult↗

PubMed1996

VIP decelerates non-REM-REM cycles and modulates hormone secretion during sleep in men.

Centrally administered vasoactive intestinal polypeptide (VIP) promotes rapid eye movement (REM) sleep in rats, rabbits, and cats. We studied the effect of 4 x 10 micrograms VIP (expt 1, n = 7) and 4 x 50 micrograms VIP (expt 2, n = 10) administered hourly as intravenous boluses between 2200 and 0100 on sleep electroencephalogram and secretion of plasma adreno corticotropic hormone, cortisol, growth hormone, and prolactin in humans. In experiment 2, the sleep cycles were decelerated during the first three cycles because of increased duration of both REM and non-REM sleep periods, and there was a tendency to increased REM-to-non-REM ratios. With a low VIP dose, prolactin levels were decreased during the whole night, whereas, with a high dose, they were increased during the first half of the night. In experiment 2, the cortisol nadir was advanced, after midnight the serum cortisol levels were enhanced, and the growth hormone peak was blunted. It appears that VIP may have a phase-advancing effect on sleep cycles and cortisol secretion, possibly through actions that involve the suprachiasmatic nucleus.

Adrenocorticotropic Hormone↗

PubMed1996

Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promoting slow-wave sleep (SWS).

It has been suggested that growth hormone (GH)-releasing hormone (GHRH) stimulates the surge in GH and enhances slow-wave sleep (SWS), two phenomena that characterize the beginning of nocturnal sleep. However, in human studies the effects of systemic GHRH administration on sleep were not consistent. This may reflect the differential influence of administration procedures being episodic in one of the above studies, but either a continuous infusion or a single bolus in the others. The present study in healthy volunteers compared changes in nocturnal sleep following 200 micrograms GHRH administered iv either episodically (4 boluses of 50 micrograms each at 2200, 2300, 2400, and 0100 h) or as a continuous infusion (57 micrograms/h between 2130 and 0100 h). Time spent in stage 4 of SWS on nights of episodic GHRH administration significantly exceeded that on nights of continuous GHRH administration (P < 0.01). Compared with a placebo condition, episodic administration of GHRH enhanced SWS (P < 0.01) and rapid eye movement (REM) sleep (P < 0.05) and diminished time spent in wakefulness and sleep stage 1 (P < 0.05). Effects of continuous GHRH infusion on sleep generally remained insignificant compared with placebo. Plasma GH concentrations were enhanced during both conditions of GHRH administration (P < 0.01), with the increase following episodic administration slightly exceeding that during continuous infusion (P < 0.05). The results support a greater physiological efficacy of episodic GHRH stimulation in promoting sleep.

Adult↗

PubMed1996

[The role of neuropeptides in normal and disordered sleep regulation].

The neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) play a key role in sleep endocrine regulation. After pulsatile application of GHRH during the first few hours of the night in young normal controls SWS and GH increase, whereas cortisol is blunted. CRH however prompts inverse effects. The balance between these peptides is changed in favour of CRH physiologically during the second time of the night, during the acute episode of depression (due to overactivity of GRH) and in the elderly (due to reduced activity of CHRH). These changes explain the aberrances of sleep endocrine activity in these states, as shallow sleep, low GH and enhanced cortisol.

Adult↗

PubMed1995

[Physiology and pathophysiology of sleep].

Human sleep is characterized by the cyclic occurrence of nonREM and REM periods and by distinct patterns of nocturnal hormone secretion. A host of factors may result in disturbed sleep, including normal aging and depression. In both states, similar changes in sleep-endocrine activity occur, including decreases in slow wave sleep and in growth hormone secretion. Preclinical investigations and studies by our laboratory in young and elderly normal controls and in patients with depression demonstrate that neuropeptides play a key role in sleep regulation. As an example, growth hormone-releasing hormone (GHRH) is a common stimulus of slow wave sleep and growth hormone release, whereas corticotropin-releasing hormone (CRH) exerts opposite effects. We suggest that an imbalance of both peptides in favor of CRH contributes to changes in sleep-endocrine activity during depression and aging.

Adult↗

PubMed1995

[Pathophysiology of sleep].

Disturbed sleep is a frequent concomitant of depression and of normal aging. Simultaneous investigations of sleep EEG and of nocturnal hormone secretion reveal that under both conditions slow-wave sleep and growth-hormone secretion decrease and sleep continuity is disturbed in comparison to younger normal controls. Animal studies and recent data from investigations in our laboratory in young and elderly normal controls and in patients with depression demonstrate that the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) are common regulators of peripheral hormone secretion and of sleep structure. We suggest that changes of the ratio between both peptides play a key role in the pathophysiology of sleep endocrine aberrations during aging and depression.

Adult↗