A good night’s sleep is doing a lot more work than most people realise. It helps rebuild the body, supports muscle and bone growth, burns fat, and for teenagers, it is tied to reaching full height potential.
At the centre of that process is growth hormone, which surges during sleep. Scientists have long known that poor sleep, especially early deep non-REM sleep, is linked to lower levels of the hormone. Now researchers at the University of California, Berkeley, say they have identified the brain circuits behind that link.
In a study published in Cell, the team mapped the circuits that control growth hormone release during sleep and identified what they describe as a new feedback system that keeps those levels in balance.
The researchers said the finding gives a clearer view of how sleep and hormones work together. They also said it could help guide future treatments for sleep disorders linked to 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.”
The study points to a system deep in the hypothalamus, a part of the brain shared by all mammals. In that region, specialised neurons release signals that either trigger or suppress growth hormone.
Two of those signals are growth hormone releasing hormone, or GHRH, which stimulates release, and somatostatin, which inhibits it. The researchers said the two work together to coordinate hormone activity across the sleep-wake cycle.
Once growth hormone enters the system, it activates the locus coeruleus, a brainstem region involved in alertness, attention and cognitive function. Disruptions in that area are linked to a range of neurological and psychiatric 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.”
To study the system, the researchers recorded brain activity in mice using electrodes and stimulated neurons with light. Because mice sleep in short bursts during the day and night, the team said they were able to get a detailed view of how growth hormone shifts across sleep stages.
They found that GHRH and somatostatin behave differently in REM and non-REM sleep.
During REM sleep, both hormones increase, leading to a surge in growth hormone. During non-REM sleep, somatostatin drops while GHRH rises more modestly, which still boosts hormone levels but in a different pattern.
The team also identified a feedback loop linking growth hormone to wakefulness. As sleep continues, growth hormone gradually builds up and stimulates the locus coeruleus, pushing the brain toward waking.
The researchers said the system has another layer. When the locus coeruleus becomes too active, it can instead trigger sleepiness, creating what they described as a delicate balance between sleep and alertness.
“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 drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health.”
Ding said the hormone’s effects may go beyond physical growth.
“Growth hormone not only helps you build your muscle and bones and reduce your fat tissue, but may also have cognitive benefits, promoting your overall arousal level when you wake up,” Ding said.
The research was supported by the Howard Hughes Medical Institute and the Pivotal Life Sciences Chancellor’s Chair fund. Yang Dan holds the Pivotal Life Sciences Chancellor’s Chair in Neuroscience. The study also included collaborators from UC Berkeley and Stanford University.
