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1.
Psychoneuroendocrinology ; 33(4): 497-506, 2008 May.
Article in English | MEDLINE | ID: mdl-18329818

ABSTRACT

Ghrelin activates the somatotropic and the hypothalamic-pituitary-adrenal axes, being crucially involved in sleep regulation. Simplified, growth hormone releasing hormone (GHRH) increases slow-wave sleep and REM sleep in males, whilst corticotropin-releasing hormone (CRH) increases wakefulness and decreases REM sleep. Ghrelin's role in sleep regulation and particularly its interactions with GHRH and CRH are not entirely clear. We aimed to elucidate the interactions between ghrelin, GHRH and CRH in sleep regulation and the secretion of cortisol and GH. Nocturnal GH and cortisol secretion and polysomnographies were determined in 10 healthy males (25.7+/-3.0 years) four times, receiving placebo (A), ghrelin (B), ghrelin and GHRH (C), or ghrelin and CRH (D) at 22:00, 23:00, 00:00, and 01:00h, in this single-blind, randomized, cross-over study. Non-REM sleep was significantly (p<0.05) increased in all verum conditions (mean+/-SEM: B: 355.3+/-7.4; C: 365.4+/-8.1; D: 371.4+/-3.9min) compared to placebo (336.3+/-6.8min). REM sleep was decreased (B: 84.3+/-4.2 [p<0.1]; C: 74.2+/-7.0 [p<0.05]; D: 80.4+/-2.7min [p<0.05]) compared to placebo (100.9+/-8.3). CRH+ghrelin decreased the time spent awake and enhanced the sleep efficiency; furthermore, the REM latency was decreased compared to the other treatment conditions. CRH enhanced the ghrelin-induced cortisol secretion but had no relevant effect on GH secretion. In turn, GHRH enhanced the ghrelin-induced GH secretion but had no effect on cortisol secretion. In conclusion, ghrelin exhibited distinct sleep effects, which tended to be enhanced by both GHRH and CRH. CRH had sleep-improving and REM permissive effects when co-administered with ghrelin, being in contrast to the effect of CRH alone in previous studies.


Subject(s)
Corticotropin-Releasing Hormone/physiology , Ghrelin/physiology , Growth Hormone-Releasing Hormone/physiology , Sleep Stages/physiology , Wakefulness/physiology , Adult , Corticotropin-Releasing Hormone/administration & dosage , Cross-Over Studies , Drug Therapy, Combination , Ghrelin/administration & dosage , Growth Hormone/blood , Growth Hormone-Releasing Hormone/administration & dosage , Humans , Hydrocortisone/blood , Male , Polysomnography , Reference Values , Single-Blind Method , Sleep Stages/drug effects , Wakefulness/drug effects
2.
Psychoneuroendocrinology ; 32(8-10): 1021-7, 2007.
Article in English | MEDLINE | ID: mdl-17850984

ABSTRACT

In young male subjects peripherally administered growth hormone-releasing hormone (GHRH) enhances GH and slow wave sleep (SWS) and blunts cortisol. In contrast, in a sample of females 19-76-year old, GHRH impairs sleep and enhances adrenocorticotropic hormone (ACTH) and cortisol. In the latter study, the days of investigation were not adapted to the menstrual cycle and premenopausal and postmenopausal women as well were included. Placebo and GHRH were given during consecutive nights. In order to confirm or reject the sexual dimorphism of the effects of GHRH on sleep we applied an improved study design. In the present study we examined the effect of pulsatile administration of two dosages of GHRH (4x25 or 4x50 microg intravenously, respectively) on sleep electroencephalogram (EEG) and nocturnal hormone secretion in healthy young women according to a randomized schedule. To rule out the influence of gonadal hormone activity, the study was adapted to the phase of the menstrual cycle and was performed at 4-6th day of menstrual cycle. A carry-over effect was excluded by the interval of at least 4 weeks between examinations. Compared to placebo rapid-eye-movement sleep decreased during the first half of the night after 4x25 microg GHRH and sleep stage 4 decreased after 4x50 microg GHRH. After both dosages GH increased whereas ACTH and cortisol remained unchanged. This study confirms that systemic GHRH impairs sleep in women.


Subject(s)
Growth Hormone-Releasing Hormone/pharmacology , Sleep/drug effects , Adrenocorticotropic Hormone/blood , Adult , Circadian Rhythm/drug effects , Electroencephalography/drug effects , Female , Growth Hormone/blood , Growth Hormone-Releasing Hormone/administration & dosage , Health , Humans , Hydrocortisone/blood , Infusions, Intravenous , Placebos
3.
Neuropsychopharmacology ; 31(4): 832-44, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16237393

ABSTRACT

The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.9+/-4.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days -3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day -3. The Hamilton Depression score decreased from 32.1+/-7.3 to 15.5+/-6.7 between days -1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin.


Subject(s)
Antidepressive Agents, Tricyclic/therapeutic use , Circadian Rhythm/drug effects , Depression/drug therapy , Hormones/blood , Mianserin/analogs & derivatives , Sleep/drug effects , Adrenocorticotropic Hormone/metabolism , Adult , Animals , Area Under Curve , Body Weight/drug effects , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , Electroencephalography/methods , Endocrine System/drug effects , Female , Ghrelin , Growth Hormone/metabolism , Humans , Hydrocortisone/metabolism , Immunoradiometric Assay/methods , Leptin/metabolism , Male , Melatonin/metabolism , Mianserin/therapeutic use , Middle Aged , Mirtazapine , Peptide Hormones/metabolism , Prolactin/metabolism , Psychometrics/methods , Time Factors
4.
Neuropsychopharmacology ; 30(6): 1187-92, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15688086

ABSTRACT

Ghrelin, a growth hormone (GH) secretagogue receptor ligand was isolated from the stomach and hypothalamus of rats and humans. In rodents, ghrelin exerts distinct orexigenic action, probably as counterpart of the anorexigenic leptin. In humans, ghrelin infusion enhances appetite. It is unknown whether single intravenous (i.v.) injections of ghrelin affect human eating behavior. Therefore, we investigated the influence of a single i.v. bolus injection of 100 microg ghrelin on appetite, ideas about food, hormone levels, and glucose concentration in young control subjects. In order to test gender differences, we included five women and four men. After ghrelin administration, appetite was enhanced in eight of nine subjects. Seven probands reported a vivid, plastic image of their preferred meal. Furthermore, ghrelin stimulated an immediate increase in plasma levels of GH (area under the curve, mean+/-SEM 35+/-16 ng/ml x min after placebo [P] to 2808+/-533 ng/ml x min after ghrelin [G]; p<0.001), cortisol (5908+/-984 ng/ml x min [P] to 10179+/-1293 ng/ml x min [G]; p<0.001), and ACTH (922+/-103 pg/ml x min [P] to 3030+/-763 pg/ml x min [G]; p<0.02), whereas leptin levels remained unchanged. Contrary to placebo, glucose concentration did not decrease markedly after administration of ghrelin. Our data suggest that i.v. ghrelin stimulates appetite and images of food in young women and men. Obviously, leptin is not involved in these effects.


Subject(s)
Adrenocorticotropic Hormone/blood , Appetite Stimulants , Food , Human Growth Hormone/blood , Hydrocortisone/blood , Imagination/drug effects , Leptin/blood , Peptide Hormones/pharmacology , Adult , Aging/psychology , Blood Glucose/metabolism , Body Weight/physiology , Female , Ghrelin , Humans , Hunger/drug effects , Individuality , Injections, Intravenous , Male , Peptide Hormones/adverse effects , Sex Characteristics
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