In Addition To Its Influence On Food Intake And Weight Gain, The Body’s Hormone Ghrelin Is A Sleep-Promoting Factor

New study may have implications for millions in search of the elusive “good night’s sleep”

March 18, 2003 (Bethesda, MD) -- In movies and novels alike, much is made of the stage of sleep known as rapid eye movement (REM), since this is the phase of slumber in which dreams (good, bad, exotic) occur.  Among the medical community, there is an increased appreciation for what is called “slow-wave” sleep, (also known as deep or delta-wave sleep), because this fourth stage of sleep can be difficult to attain. If one is awakened during the first three stages of sleep, they must repeat these stages again before reaching fourth stage or “delta-wave,” sleep.

Once this latter stage is reached, muscles are relaxed, blood pressure drops, and the pulse and breathing are slower.  According to the Sleep Research Center, other benefits to the body are accrued during slow-wave sleep, including: an increase of blood supply to the body; a decrease in body temperature thus preserving energy; a lowering of metabolic activity enabling tissue repair and growth; an increase of natural immune-system modulators; and a period in which the growth hormone secretions reach their peak, thus stimulating body growth and development.

A New Study

A team of researchers has found that the peptide hormone ghrelin, bound to the growth hormone secretagogue (GHS) receptor, has a distinct positive action on stage four sleep and nocturnal hormone secretion.  Their findings suggest that, in addition to its influence on growth hormone secretion, food intake, and weight gain, ghrelin is a sleep-promoting factor. This new role for the peptide appears to be complementary in function to its established function in the regulation of energy balance and obesity.

Previous rat studies offered conflicting data on sleep following ghrelin administration. In one study, a decrease of REM sleep was found after administration of ghrelin to rats. In another study, ghrelin was given to two different strains of mice, intact animals and those with nonfunctional growth hormone-releasing hormone receptors. Only in mice with intact growth hormone-releasing hormone receptors did NREM sleep increase after administration of the peptide.

Prior to this research, the influence of ghrelin on human sleep was unknown. A team of German researchers selected a protocol that followed previous studies on the sleep-endocrine effects of the peptide, including growth hormone-releasing hormone, GHRP-6, hexarelin, and vasoactive intestinal peptide (VIP).   They investigated the effects of the systematic administration of ghrelin on sleep EEG and of GH, ACTH, cortisol, and leptin in healthy male subjects.  The authors of “Ghrelin Promotes Slow-Wave Sleep in Humans” are J. C. Weikel, A. Wichniak, M. Ising, H. Brunner, E. Friess, K. Held, S. Mathias, D. A. Schmid, M. Uhr, and A. Steiger, all from the Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Germany.  Their findings appear in the February 2003 edition of the American Journal of Physiology-Endocrinology and Metabolism.

Methodology

Subjects in this study were healthy male volunteers, all free of alcohol, tobacco, and caffeine abuse. The sleep-endocrine studies consisted of two sessions, separated by one week in which a placebo (saline) or ghrelin was administered according to a double-blind, randomized schedule. The experimental sessions consisted of two successive nights in the sleep laboratory.  The first night allowed adaptation to the laboratory setting. On the second night, a dose of ghrelin or placebo was administered as a bolus injection through an indwelling intravenous catheter, which permitted administration of the testing drug and repeated blood collection in the adjacent laboratory without disturbing the study subject.

All subjects were reclining at 8:00 PM.  Injections of ghrelin or placebo were given hourly between 10:00 PM and 1:00 AM.  Blood samples were collected every 30 minutes between 8:00 and 10:00 PM, and every 20 minutes between 10:00 PM and 7:00 AM.  The subjects were not allowed to sleep until the lights were turned off at 11:00 PM.  Polysomnographic recordings were obtained from 11:00 PM to 7:00 AM, and consisted of two EEGs, vertical and horizontal electroculograms, and electromyogram.  A hormone analysis was conducted with the drawn blood samples.

Results 

On the night of ghrelin administration, the time spent in slow-wave or stage IV sleep increased significantly compared with the placebo night. Separate inspections of the three sleep-time segments showed significant increases of slow-wave sleep during the first and second thirds of the night but not during the last third.  REM sleep showed a significant decrease only during the second third of the night. Intermittent wakefulness appeared to decrease, although it did not reach a level of significance. All other sleep continuity and sleep architecture variables remained unchanged.

Conclusions

This study finds that the body’s endocrine system may offer a means for the body to obtain deep sleep, that which contributes to the body’s overall health. These findings could have important implications for long-term health, since the pursuit of a “good night’s sleep” is an obsession for many Americans. 

Source: February 2003 edition of the American Journal of Physiology-Endocrinology and Metabolism.

 -end-

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

***

Editor’s Note: To set up an interview with a member of the research team, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.