Scientists have long known that sleep deprivation can interfere with growth hormone production. What remained unclear was how the brain controls this process, particularly during non-REM sleep—the deep, restorative phase that typically dominates the early part of the night.

Now, researchers at the University of California, Berkeley, have uncovered the brain circuitry behind the relationship between sleep and growth hormone. In a study published in the journal Cell, the team identified neurons that regulate growth hormone release during sleep and discovered a previously unknown feedback system that helps balance hormone levels and wakefulness.

The findings show that the relationship works both ways: sleep stimulates growth hormone production, while growth hormone sends signals back to the brain that influence when a person wakes up.

The discovery could eventually help scientists develop new approaches for treating sleep disorders associated with metabolic diseases such as diabetes and neurological diseases such as Parkinson’s and Alzheimer’s disease.

“People know that growth hormone release is closely related to sleep, but only by taking blood samples during sleep and checking growth hormone levels,” said Xinlu Ding, lead author of the study and a postdoctoral fellow in the Department of Neuroscience and Helen Wills Neuroscience Institute at the University of California, Berkeley. “We’re actually directly recording neural activity in mice to see what’s going on. We’re providing the basic circuitry that we can work on to develop a variety of treatments in the future.”

Why deep sleep matters for growth and metabolism

Although growth hormone is best known for its role in childhood development, it remains important during adulthood. It supports muscle and bone maintenance, helps regulate how the body uses stored fat, and influences blood sugar levels.

Continuously disrupted sleep can negatively affect growth hormone regulation. Because the hormone helps control glucose and fat metabolism, sleep deprivation may contribute to an increased risk of obesity, diabetes, and cardiovascular disease.

To understand how the brain coordinates these processes, Berkeley researchers focused on the hypothalamus. This small but important control center, located deep in the brain, helps regulate hunger, body temperature, hormone production, and daily sleep-wake cycles. Its basic functions have been conserved throughout mammalian evolution.

The researchers examined two types of neurons in the hypothalamus: neurons that produce growth hormone-releasing hormone, or GHRH, and neurons that produce somatostatin.

These chemical messengers have opposing functions. GHRH promotes growth hormone secretion, while somatostatin suppresses it. Together, they help control how much growth hormone enters the bloodstream by regulating the release of growth hormone from the pituitary gland, a small hormone-producing structure at the base of the brain.

Scientists also investigated how growth hormone affects the locus coeruleus, a brainstem region involved in alertness, attention, thinking ability, and the willingness to explore new and unfamiliar experiences. Disruptions in this region’s activity are thought to be associated with several psychiatric and neurological disorders.

“Understanding the neural circuitry of growth hormone release may ultimately lead to new hormonal therapies that improve sleep quality and restore normal growth hormone balance,” said study co-author Daniel Silverman, a postdoctoral fellow at the University of California, Berkeley. “There are several experimental gene therapies that target specific cell types. This circuit could be a new handle for reducing excitability in the locus coeruleus, which has not been talked about until now.”

Scientists map the brain circuits that control growth hormone

The research was conducted in the lab of Yan Dunn, a professor of neuroscience and molecular cell biology at the University of California, Berkeley.

To investigate how the circuit works, the research team studied mice using electrodes implanted in their brains. The researchers used light to stimulate specific neurons in the hypothalamus while recording neural activity, allowing them to observe how different parts of the system responded.

Mice are useful for studying sleep regulation because their sleep patterns differ significantly from those of humans. Rather than sleeping in one long period each night, mice typically sleep in short periods lasting only a few minutes throughout the day and night.

This gave researchers repeated opportunities to examine how neural activity and growth hormone regulation changed as the animals moved between sleep and wakefulness.

Using advanced technology to track connections between brain cells, the team discovered that GHRH and somatostatin behave differently depending on the stage of sleep.

How REM and non-REM sleep affect growth hormone

During rapid eye movement, or REM, sleep—a stage commonly associated with vivid dreams—activity involving both GHRH and somatostatin increases. Although these hormones normally have opposing effects, their coordinated activity during this stage contributes to increased growth hormone release.

The pattern changes during non-REM sleep. Somatostatin activity decreases and its inhibitory effect is reduced, while GHRH activity increases moderately. This combination also stimulates growth hormone secretion.

The finding helps explain how different sleep stages can support the release of the same essential hormone through distinct patterns of brain activity.

Growth hormone also helps control when you wake up

Perhaps the most surprising discovery was that growth hormone does not simply respond to signals from the sleeping brain. It also affects brain circuits that control arousal.

As growth hormone gradually accumulates during sleep, it stimulates neurons in the locus coeruleus to increase their activity and facilitate the transition to wakefulness.

This creates a feedback loop: sleep promotes growth hormone release, and the resulting hormonal activity helps regulate the sleep-wake cycle.

Researchers also identified unexpected complications. Increased activity in the locus coeruleus generally promotes arousal, but excessive stimulation can have the opposite effect.

In an earlier study published in the same year, Silverman demonstrated that when neurons in this region become overexcited, they can paradoxically promote drowsiness rather than alertness.

Taken together, the 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-regulation as homeostasis—the body’s ability to maintain a stable internal state even as environmental and physiological demands change.

“This suggests that sleep and growth hormone form a tightly balanced system. Too little sleep can reduce the release of growth hormone, and too much growth hormone can conversely push the brain toward a state of wakefulness,” Silverman said. “Sleep promotes the release of growth hormone, which feeds back to regulate wakefulness. This balance is essential for growth, repair, and metabolic health.”

The surprising connection between sleep and brain health

The newly identified feedback system may affect more than physical growth and metabolism.

Because the locus coeruleus helps regulate attention, alertness, and cognitive function, the effects of growth hormone on this region may also influence brain function after waking.

This raises the possibility that maintaining healthy sleep and growth hormone rhythms supports both physical recovery and mental performance.

“Growth hormone not only helps build muscle and bone and reduce fat tissue, but it also promotes your overall level of alertness when you wake up and may have benefits for cognitive function,” Ding said.

By identifying the specific brain cells and signaling pathways involved, the researchers provided a foundation for exploring treatments that target sleep and hormonal dysregulation.

Such an approach could eventually prove useful for people with sleep disorders associated with metabolic or neurological diseases. However, the experiment was conducted in mice, and additional research will be needed to determine how these mechanisms work in humans and whether they can be safely targeted for treatment.

The findings highlight a fundamental principle of sleep biology: rest is more than a time to switch off the brain. Sleep is an active, carefully regulated process in which hormones and neural circuits communicate continuously to support growth, repair, metabolism, and alertness.

Research funding and contributors

This research was supported by the Howard Hughes Medical Institute (HHMI) and the Pivotal Life Sciences Chancellor’s Chair Fund, which supported Dunn as an HHMI investigator until the year of publication.

Dan holds the Life Sciences Dean’s Chair, a pivotal position in the field of neuroscience.

Other co-authors include Peng Zhong, Bing Li, Chenyan Ma, Lihui Lu, Grace Jiang, Zhe Zhang, Xiaolin Huang, Xun Tu, Zhiyu Melissa Tian of the University of California, Berkeley, and Fuu-Jiun Hwang and Jun Ding of Stanford University.