A good night’s sleep does much more than leave you feeling refreshed. It also triggers the release of growth hormone, a key hormone that helps build muscle and bones, burn fat, and promote healthy growth. That’s why athletes value quality sleep for recovery and why teenagers need enough sleep to reach their full height potential.
Scientists have long known that growth hormone levels increase during sleep, especially during deep, non-REM sleep. What’s not clear is exactly how the brain controls this process.
Now, researchers at the University of California, Berkeley have discovered the brain circuit responsible for regulating growth hormone during sleep. His study, published in the journal CellIt also reveals a previously unknown feedback system that helps keep growth hormone levels in balance.
The discovery offers new insights into the close relationship between sleep and hormonal regulation. Over time, it could guide new treatments for sleep disorders linked to metabolic diseases such as diabetes, as well as neurodegenerative conditions, including Parkinson’s and Alzheimer’s disease.
“People know that growth hormone release is closely related to sleep, but only by drawing blood and monitoring growth hormone levels during sleep,” said the study’s first author, Xinlu Ding, a postdoctoral fellow in the Department of Neuroscience at UC Berkeley and the Helen Wills Neuroscience Institute. “We are actually directly recording neuronal activity in mice to see what is happening. We are providing a basic circuit to work on in the future to develop different treatments.”
Because growth hormone also helps regulate glucose and fat metabolism, consistently poor sleep can increase your risk of obesity, diabetes, and cardiovascular disease.
How the brain controls growth hormone during sleep
The nerve cells that coordinate the release of growth hormone are located deep in the hypothalamus, an ancient brain region found in mammals. These include growth hormone-releasing hormone (GHRH) neurons, along with two different types of somatostatin neurons.
Once growth hormone is released, it activates neurons in the locus coeruleus, a region of the brain stem involved in alertness, attention, thinking, and responding to new experiences. Problems affecting the locus coeruleus have been linked to numerous neurological and psychiatric disorders.
“Understanding the neural circuitry for growth hormone release could eventually point toward new hormone therapies to improve sleep quality or restore normal growth hormone balance,” said Daniel Silverman, a UC Berkeley postdoctoral fellow and co-author of the study. “There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel way to try to reduce the excitability of the locus coeruleus, something that hasn’t been talked about before.”
Mapping the sleep growth hormone circuit
Working in the lab of Yang Dan, a professor of neuroscience and molecular and cellular biology at UC Berkeley, the research team studied brain circuits in mice by placing electrodes in their brains and stimulating hypothalamic neurons with light while recording neuronal activity.
Mice naturally sleep in short bursts lasting only a few minutes during the day and night. That pattern allowed the researchers to repeatedly observe changes in growth hormone activity over many sleep-wake cycles.
Using advanced circuit tracing techniques, the team discovered that the two peptide hormones responsible for regulating growth hormone release behave differently depending on the stage of sleep. GHRH promotes the release of growth hormone, while somatostatin suppresses it.
During REM sleep, both GHRH and somatostatin increase, leading to greater growth hormone release. However, during non-REM sleep, somatostatin levels fall while GHRH increases only moderately, creating a different pattern of hormonal regulation.
A feedback loop that balances sleep and wakefulness
The researchers also identified a previously unknown feedback mechanism involving the locus coeruleus.
As growth hormone gradually builds up during sleep, it stimulates the locus coeruleus and promotes wakefulness. But if activity in the locus coeruleus becomes too high, it unexpectedly begins to promote drowsiness, a finding Silverman reported earlier this year.
“This suggests that sleep and growth hormone form a tightly balanced system: too little sleep reduces the release of growth hormone, and too much growth hormone can, in turn, push the brain toward wakefulness,” Silverman said. “Sleep drives the release of growth hormone, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair, and metabolic health.”
Because growth hormone influences the locus coeruleus, which plays a central role in maintaining alertness during the day, this newly identified system may also affect attention and other aspects of cognitive function.
“Growth hormone not only helps build muscle and bone and reduce adipose tissue, but it may also have cognitive benefits, promoting your overall level of arousal when you wake up,” Ding said.
The research was supported by the Howard Hughes Medical Institute (HHMI), which, until this year, supported Dan as an HHMI investigator, and the Pivotal Life Sciences Chancellor’s Chair fund. Dan is the Chancellor’s Chair in Neuroscience at Pivotal Life Sciences. 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, along with Fuu-Jiun Hwang and Jun Ding of Stanford University.