Slow-wave sleep loss and cardiometabolic dysfunction: androgenic hormone secretion as a critical intermediate mediator

abstract 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.

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Suppression of nocturnal growth hormone secretion in epilepsy with continuous spike-waves during slow-wave sleep

Pediatrics International ◽

10.1046/j.1442-200x.1999.4121029.x ◽

1999 ◽

Vol 41 (2) ◽

pp. 192-194 ◽

Cited By ~ 1

Author(s):

Kuniaki Iyoda ◽

Hitoshi Tobiume ◽

Susumu Kanzaki ◽

Syouko Takano2 And Yoshiki Seino

Keyword(s):

Growth Hormone ◽

Slow Wave ◽

Slow Wave Sleep ◽

Hormone Secretion ◽

Growth Hormone Secretion

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Ghrelin promotes slow-wave sleep in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00184.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. E407-E415 ◽

Cited By ~ 162

Author(s):

J. C. Weikel ◽

A. Wichniak ◽

M. Ising ◽

H. Brunner ◽

E. Friess ◽

...

Keyword(s):

Slow Wave ◽

Slow Wave Sleep ◽

Hormone Secretion ◽

Wave Activity ◽

Sleep Eeg ◽

Endogenous Ligand ◽

Plasma Gh ◽

Electroencephalogram Eeg ◽

Inverse Pattern ◽

Ghs Receptor

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 × 50 μg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans ( n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated δ-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200–0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.

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An essential role for MEF2C in the cortical response to loss of sleep

10.1101/2020.04.27.064535 ◽

2020 ◽

Author(s):

Theresa E. Bjorness ◽

Ashwinikumar Kulkarni ◽

Volodymer Rybalchenko ◽

Ayako Suzuki ◽

Catherine Bridges ◽

...

Keyword(s):

Gene Expression ◽

Slow Wave ◽

Transcriptional Activity ◽

Slow Wave Sleep ◽

Sleep Loss ◽

Wave Activity ◽

Altered Gene Expression ◽

Mepsc Frequency ◽

Differential Gene ◽

Altered Gene

AbstractNeuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.One Sentence SummaryMEF2C is critical to the response to sleep loss.

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Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men.

Journal of Clinical Investigation ◽

10.1172/jci119587 ◽

1997 ◽

Vol 100 (3) ◽

pp. 745-753 ◽

Cited By ~ 155

Author(s):

E Van Cauter ◽

L Plat ◽

M B Scharf ◽

R Leproult ◽

S Cespedes ◽

...

Keyword(s):

Growth Hormone ◽

Slow Wave ◽

Slow Wave Sleep ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Young Men ◽

Simultaneous Stimulation ◽

Gamma Hydroxybutyrate ◽

Stimulation Of

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PHYSIOLOGICAL GROWTH HORMONE SECRETION DURING SLOW-WAVE SLEEP IN SHORT PREPUBERTAL CHILDREN

Clinical Endocrinology ◽

10.1111/j.1365-2265.1987.tb01162.x ◽

1987 ◽

Vol 27 (3) ◽

pp. 355-361 ◽

Cited By ~ 11

Author(s):

P. ADLARD ◽

F. BUZI ◽

J. JONES ◽

R. STANHOPE ◽

M. A. PREECE

Keyword(s):

Growth Hormone ◽

Slow Wave ◽

Slow Wave Sleep ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Prepubertal Children

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Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep

Acta Endocrinologica ◽

10.1530/eje.0.1510561 ◽

2004 ◽

pp. 561-566 ◽

Cited By ~ 10

Author(s):

SK Jessup ◽

BA Malow ◽

KV Symons ◽

AL Barkan

Keyword(s):

Growth Hormone ◽

Slow Wave ◽

Hormone Receptors ◽

Slow Wave Sleep ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Nrem Sleep ◽

Temporal Association ◽

Sleep Stages ◽

Sleep Study

OBJECTIVES: A temporal association between non-rapid eye movement (NREM) sleep stages 3 and 4 and nocturnal augmentation of GH release was found long ago, yet the precise mechanism for this association has not been identified. It has been shown, however that pulsatile GHRH administration increases both slow-wave sleep (SWS) and GH. Based on these data, a role for GHRH as an inducer of SWS was proposed. To test this hypothesis, we have performed the corollary experiment whereby the action of endogenous GHRH has been antagonized. DESIGN: Healthy men (20-33 years old) had an infusion of GHRH antagonist ((N-Ac-Tyr(1), D-Arg(2)) GHRH-29 (NH(2))) or saline for a 12-h period, between 2100 and 0900 h. An i.v. bolus of GHRH was given at 0700 h and GH samples were drawn from 0700 to 0900 h to document the efficacy of GH suppression by the GHRH antagonist. METHODS: A limited montage sleep study was recorded from 2300 to 0700 h during each admission. Plasma GH concentrations were analyzed by the use of a sensitive chemiluminometric assay. RESULTS: Effectiveness of the GHRH antagonist was validated in all subjects by demonstrating 93+/-1.8% (P=0.012) suppression of GH response to a GHRH bolus. Polysomnography demonstrated that the percentage of SWS was not different when saline and GHRH antagonist nights were compared (P=0.607); other quantifiable sleep parameters were also unchanged. CONCLUSIONS: We conclude that endogenous GHRH is indispensable for the nocturnal augmentation of GH secretion, but that it is unlikely to participate in the genesis of SWS.

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An essential role for MEF2C in the cortical response to loss of sleep in mice

eLife ◽

10.7554/elife.58331 ◽

2020 ◽

Vol 9 ◽

Author(s):

Theresa E Bjorness ◽

Ashwinikumar Kulkarni ◽

Volodymyr Rybalchenko ◽

Ayako Suzuki ◽

Catherine Bridges ◽

...

Keyword(s):

Gene Expression ◽

Slow Wave ◽

Transcriptional Activity ◽

Slow Wave Sleep ◽

Sleep Loss ◽

Wave Activity ◽

Altered Gene Expression ◽

Mepsc Frequency ◽

Differential Gene ◽

Altered Gene

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

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