Reciprocal interactions between the GH axis and sleep

doi:10.1016/j.ghir.2004.03.006

Growth Hormone & IGF Research

Volume 14, Supplement, June 2004, Pages 10-17

https://doi.org/10.1016/j.ghir.2004.03.006 Get rights and content

Abstract

For more than 30 years, growth hormone (GH) has been observed to be preferentially secreted during deep, slow-wave sleep (SWS). However, the mechanisms that underlie this robust relationship that links anabolic processes in the body with behavioral rest and decreased cerebral metabolism remain to be elucidated. Current evidence indicates that GH secretion during the beginning of sleep appears to be primarily regulated by GH-releasing hormone (GHRH) stimulation occurring during a period of relative somatostatin withdrawal, which also is associated with elevated levels of circulating ghrelin. Apparently, two populations of GHRH neurons need to be simultaneously active to stimulate, in a coordinated fashion, SWS and pituitary GH release. Pharmacological interventions that are capable of increasing the duration and/or the intensity of SWS such as oral administration of γ-hydroxybutyrate (GHB), also increase the rate of GH release. Because the normal negative feedback exerted by GH on central GHRH is inoperative in patients with GH deficiency, it is possible that the decreased energy levels and fatigue often reported by GH-deficient adults partly reflect an alteration in sleep–wake regulation. Preliminary data from a sleep study of adults with GH deficiency using wrist actigraphy for 6 nights at home and polysomnography in the laboratory indeed show decreased total sleep time and increased sleep fragmentation in GH-deficient patients as compared with normal controls.

Section snippets

Sleep: an introduction

In The Iliad, Homer stated that “Sleep and death are twin brothers,” and as late as 1834, the Scottish physiologist McNish wrote: “Sleep is the intermediate state between wakefulness and death.” Until the middle of the 20th century, the prevailing notion was that sleep occurs as a result of withdrawal of activity in systems that promote wakefulness. Studies conducted in the late 1940s and early 1950s disproved this concept and demonstrated that sleep involves two states of distinct brain

The relationship between nocturnal GH secretion and sleep

In the late 1960s, well-documented studies involving analyses of polygraphically recorded sleep and concomitant GH levels indicated that there is a consistent relationship between the appearance of delta waves on the EEG and GH secretion, particularly during early sleep (for review see [5]). Later studies of the relationship between sleep stages and GH release used deconvolution (a procedure which allows secretory rates to be derived from plasma concentrations by eliminating the effects of

Putative mechanisms linking GH secretion and sleep

Although the observation that GH is preferentially secreted during deep sleep is now more than 30 years old, the mechanisms that underlie this robust relationship remain largely unknown. As noted by Obal and Krueger [17], the significance of this relationship is that anabolic processes in the body are synchronized to a state when behavioral rest occurs and when cerebral glucose use is at its lowest point.

Sleep-onset GH secretion appears to be primarily regulated by GHRH stimulation occurring

Sleep–wake regulation in adult GH deficiency

Improvements in indices of “quality of life” are one of the most consistent outcomes of treatment with exogenous GH of adult subjects with GH deficiency. Improvements in quality of life could partly reflect a normalization of sleep quality resulting in increased daytime alertness and vigor. Experienced clinicians often report anecdotal evidence of excessive daytime sleepiness in GH-deficient adults. However, only a limited number of studies of nocturnal sleep in GH-deficient adults have been

Acknowledgements

We gratefully acknowledge the intellectual input of Dr. Barbara Lippe and Dr. Linda Fryklund in the design and interpretation of our study of sleep–wake regulation in adults with GH deficiency.

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^☆: Supported in part by grants from the National Institute on Aging (PO1 AG-11412) and from Pharmacia Corporation (307 MET-0018-052). Clinical studies performed in the General Clinical Research Center of the University of Chicago were supported by Grant MO1-RR-00055 from the National Institutes of Health.

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Reciprocal interactions between the GH axis and sleep☆

Abstract

Section snippets

Sleep: an introduction

The relationship between nocturnal GH secretion and sleep

Putative mechanisms linking GH secretion and sleep

Sleep–wake regulation in adult GH deficiency

Acknowledgements

Neuroscience

Alcohol

Brain Res.

Brain Research – Brain Res. Rev.

A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects

Activation of ventrolateral preoptic neurons during sleep

Science

Identification of sleep-promoting neurons in vitro

Nature

Interactions between growth hormone secretion and sleep

Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages

J. Clin. Endocrinol. Metab.

A quantitative estimation of GH secretion in normal man: reproducibility and relation to sleep and time of day

J. Clin. Endocrinol. Metab.

A quantitative evaluation of the relationships between growth hormone secretion and delta wave electroencephalographic activity during normal sleep and after enrichment in delta waves

Sleep

Adaptation of the 24-hour growth hormone profile to a state of sleep debt

Am. J. Physiol. (Endocrinol. Metabol.)

Nocturnal augmentation of growth hormone (GH) secretion is preserved during repetitive bolus administration of GH-releasing hormone: potential involvement of endogenous somatostatin – a clinical research center study

J. Clin. Endocrinol. Metab.

Age-dependent suppression of nocturnal growth hormone levels during sleep deprivation

Neuroendocrinology

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men

Sleep

Pharmacology of classic and novel hypnotic drugs

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

Sleep

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

J. Clin. Invest.

Biochemical regulation of non-rapid-eye-movement sleep

Front. Biosci.

Nocturnal growth hormone (GH) secretion is eliminated by infusion of GH-releasing hormone antagonist

J. Clin. Endocrinol. Metab.

Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery [Comment]

N. Engl. J. Med.

Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep–wake patterns in rats

Endocrinology