A good night's sleep does much more than leave you feeling refreshed, as during deep sleep the body releases growth hormone, a powerful chemical messenger that helps build muscle, strengthen bones, and regulate fat metabolism, making sufficient sleep especially important for teenagers who rely on this hormone to reach their full height potential. 
While scientists have long known that insufficient sleep can interfere with growth hormone production, it remained unclear exactly how the brain controls this process, particularly during non-REM sleep, the deep, restorative stage that typically dominates the earlier part of the night. 
Now, researchers at the University of California, Berkeley, have uncovered the brain circuitry behind this relationship; in a study published in the journal Cell, the team identified the neurons that regulate growth hormone release during sleep and discovered a previously unknown feedback system that helps maintain a delicate balance between hormone levels and wakefulness. 
The discovery reveals that the relationship works in both directions: sleep stimulates growth hormone production, but growth hormone also sends signals back to the brain that influence when we wake up, findings that could eventually help scientists develop new approaches to treating sleep disorders associated with metabolic diseases such as diabetes, as well as neurological conditions including Parkinson's and Alzheimer's. 
"People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep," said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute. 
"We're actually directly recording neural activity in mice to see what's going on. We are providing a basic circuit to work on in the future to develop different treatments." Although growth hormone is best known for its role in childhood development, its importance extends well into adulthood because it supports the maintenance of muscle and bone, helps the body regulate how it uses stored fat, and influences blood sugar levels, consequently, when sleep is consistently disrupted, growth hormone regulation can suffer, and because this hormone helps control glucose and fat metabolism, inadequate sleep may contribute to an increased risk of obesity, diabetes, and cardiovascular disease. 
To understand how the brain coordinates these processes, the Berkeley researchers focused on the hypothalamus, a small but essential control center located deep within the brain that helps regulate hunger, body temperature, hormone production, and the daily cycle of sleeping and waking, functions preserved throughout mammalian evolution. 
Within the hypothalamus, they examined neurons that produce growth hormone-releasing hormone (GHRH) and two distinct types of neurons that produce somatostatin, chemical messengers with opposing functions where GHRH encourages growth hormone secretion while somatostatin suppresses it, together controlling how much growth hormone enters the bloodstream largely by regulating its release from the pituitary gland. 
The scientists also investigated how growth hormone influences the locus coeruleus, a region in the brainstem involved in alertness, attention, thinking, and the drive to explore new or unfamiliar experiences, noting that disruptions in this region's activity have been linked to several psychiatric and neurological disorders. 
"Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance," said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. "There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn't been talked about before." Conducted in the laboratory of Yang Dan, a professor of neuroscience and of molecular and cell biology at UC Berkeley, the research utilized electrodes implanted in mice brains to record neural activity while using light to stimulate specific hypothalamic neurons. 
Mice are particularly useful for studying sleep regulation because their sleep patterns differ significantly from those of humans, as rather than sleeping through one long stretch each night, mice typically sleep in brief episodes lasting only several minutes scattered throughout the day and night, giving researchers repeated opportunities to examine how neural activity and growth hormone regulation changed as the animals moved between sleeping and waking. 
Using advanced techniques to trace connections between brain cells, the team discovered that GHRH and somatostatin behave differently depending on the sleep stage: during rapid eye movement (REM) sleep, commonly associated with vivid dreaming, activity involving both hormones increases, and although they normally exert opposing effects, their coordinated activity contributes to increased growth hormone release, whereas during non-REM sleep, somatostatin activity decreases to reduce inhibitory influence while GHRH activity rises moderately, a combination that also promotes secretion. Perhaps the most surprising finding was that growth hormone does not simply respond to signals from the sleeping brain but also influences the circuits controlling wakefulness; as growth hormone gradually builds up during sleep, it stimulates neurons in the locus coeruleus, increasing their activity and helping promote the transition toward waking, creating a feedback loop where sleep encourages hormone release and the resulting activity helps regulate the sleep-wake cycle.