A good night’s sleep does more than leave you feeling refreshed. During deep sleep, the body releases growth hormone, a powerful chemical messenger that helps build muscle, strengthen bones, and regulate fat metabolism. For adolescents, getting enough sleep is especially important, as growth hormone plays a major role in reaching their full height potential.
Scientists have long known that a lack of sleep can interfere with growth hormone production. What remains unclear is exactly how the brain controls this process, particularly during non-REM sleep, the deep, restorative phase that typically dominates the start of the night.
Now, researchers at the University of California, Berkeley have discovered the brain circuits behind this relationship. In a study published in the journal CellThe team identified the neurons that regulate the release of growth hormone during sleep and discovered a previously unknown feedback system that helps maintain a delicate balance between hormone levels and wakefulness.
The finding reveals that the relationship works both ways. Sleep stimulates growth hormone production, but growth hormone also sends signals back to the brain that influence when we wake up.
The findings could potentially help scientists develop new approaches to treating sleep disorders associated with metabolic diseases such as diabetes, as well as neurological diseases such as Parkinson’s and Alzheimer’s.
“People know that growth hormone release is closely linked to sleep, but only by drawing blood and checking growth hormone levels during sleep,” said study first author Xinlu Ding, a postdoctoral researcher in the UC Berkeley Department of Neuroscience and the Helen Wills Neuroscience Institute. “In fact, we directly record neuronal activity in mice to see what is happening. We provide a basic circuit to work on in the future to develop different treatments.”
Why deep sleep is important for growth and metabolism
Growth hormone is best known for its role in childhood development, but its importance extends into adulthood. It supports the maintenance of muscles and bones, helps the body regulate how it uses stored fat, and influences blood sugar levels.
When sleep is constantly disrupted, growth hormone regulation can suffer. Because this hormone helps control glucose and fat metabolism, insufficient 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 a region called the hypothalamus. Located deep in the brain, this small but essential control center helps regulate hunger, body temperature, hormone production, and the daily sleep and wake cycle. Its fundamental functions have been preserved throughout mammalian evolution.
In the hypothalamus, the researchers looked at neurons that produce growth hormone-releasing hormone (GHRH) and two distinct types of neurons that produce somatostatin.
These chemical messengers have opposite functions. GHRH promotes growth hormone secretion, while somatostatin suppresses it. Together, they help control the amount of growth hormone that enters the bloodstream, largely by regulating its release from the pituitary gland, a small hormone-producing structure located at the base of the brain.
Scientists have also studied how growth hormone influences the locus coeruleus, a region of the brainstem involved in alertness, attention, thinking, and the willingness to explore new or unfamiliar experiences.
Disturbances in the activity of this region have been linked to several psychiatric and neurological disorders.
“Understanding the neural circuitry of growth hormone release could eventually lead to new hormonal therapies to improve sleep quality or restore normal growth hormone balance,” said Daniel Silverman, a postdoctoral researcher at UC Berkeley and co-author of the study. “There are some experimental gene therapies where you target a specific cell type. This circuit could be a new method of trying to reduce the excitability of the locus coeruleus, which has never been talked about before.”
Scientists map brain circuit that controls growth hormone
The research was conducted in the laboratory of Yang Dan, professor of neuroscience and molecular and cellular biology at UC Berkeley.
To study how the circuits worked, the team studied mice using electrodes implanted in their brains. The scientists recorded neuronal activity while using light to stimulate specific neurons in the hypothalamus, allowing them to observe how different parts of the system responded.
Mice are particularly useful for studying sleep regulation because their sleep patterns differ significantly from those of humans. Rather than sleeping for a long period each night, mice typically sleep in brief episodes lasting only a few minutes, spread throughout the day and night.
This gave the researchers repeated opportunities to examine how neuronal activity and growth hormone regulation changed as the animals moved between sleep and wakefulness.
Using advanced techniques to trace connections between brain cells, the team discovered that GHRH and somatostatin behave differently depending on sleep stage.
During rapid eye movement (REM) sleep, a stage typically associated with vivid dreams, activity involving both GHRH and somatostatin increases. Although these hormones normally exert opposing effects, their coordinated activity during this stage helps increase the release of growth hormone.
During non-REM sleep, the pattern changes. Somatostatin activity decreases, thereby reducing its inhibitory effect, while GHRH activity increases moderately. This combination also promotes growth hormone secretion.
This finding helps explain how different stages of sleep can promote the release of the same essential hormone through distinct patterns of brain activity.
Growth hormone also helps control waking
Perhaps the most surprising finding is that growth hormone doesn’t simply respond to signals from the sleeping brain. It also influences the brain circuits that control wakefulness.
As growth hormone gradually accumulates during sleep, it stimulates neurons in the locus coeruleus, increasing their activity and promoting the transition to wakefulness.
This creates a feedback loop in which sleep promotes the release of growth hormone and the resulting hormonal activity helps regulate the sleep-wake cycle.
The researchers also identified an unexpected complication. Although greater locus coeruleus activity generally promotes alertness, excessive stimulation can have the opposite effect.
In an earlier study published the same year, Silverman demonstrated that when neurons in this region become overexcited, they can paradoxically promote sleepiness rather than wakefulness.
Together, these findings reveal a carefully regulated system in which the brain must balance competing signals to maintain healthy sleep and hormonal activity.
Scientists describe this type of self-regulatory process as homeostasis, the body’s ability to maintain stable internal conditions even when its environment and physiological demands change.
“This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness,” Silverman said. “Sleep stimulates the release of growth hormone, and growth hormone responds to regulate wakefulness, and this balance is essential for growth, repair, and metabolic health.”
A surprising link between sleep and brain health
The newly identified feedback system could have implications beyond physical growth and metabolism.
Since the locus coeruleus helps regulate attention, alertness, and cognitive function, growth hormone’s influence on this region suggests that it may also play a role in the efficiency of brain function after waking.
This raises the possibility that maintaining healthy sleep and growth hormone rhythms may promote both physical recovery and mental performance.
“Growth hormone not only helps you build muscle and bones and reduce fat tissue, but may also have cognitive benefits, promoting your overall wakefulness level when you wake up,” Ding said.
By identifying the specific brain cells and signaling pathways involved, researchers have laid the foundation for exploring therapies targeting sleep disruption and hormonal regulation.
Such approaches could ultimately prove useful for people suffering from sleep disorders linked to metabolic disorders or neurological diseases. However, the experiments were conducted on mice and further research will be needed to determine how these mechanisms work in humans and whether they can be safely targeted with treatments.
The findings underscore a fundamental principle of sleep biology: rest is not simply a period when the brain turns off. It is an active, carefully coordinated process in which hormones and neural circuits constantly communicate to support growth, repair, metabolism, and arousal.
Research funding and contributors
The research was supported by the Howard Hughes Medical Institute (HHMI), which supported Dan as an HHMI investigator until the year the study was published, and by the Pivotal Life Sciences Chancellor’s Chair fund.
Dan holds the Life Sciences Chancellor’s Pivotal Chair in Neuroscience.
Other co-authors include Peng Zhong, Bing Li, Chenyan Ma, Lihui Lu, Grace Jiang, Zhe Zhang, Xiaolin Huang, Xun Tu and Zhiyu Melissa Tian of UC Berkeley, and Fuu-Jiun Hwang and Jun Ding of Stanford University.
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