Sleep is often treated as downtime, a passive break between the real business of being awake. But a new study has revealed that sleep is active, essential biology, showing how the brain uses the night to flood the body with growth hormone to repair muscles, strengthen bones and balance metabolism. Researchers have uncovered the neural circuitry that explains why growth hormone surges during shut-eye, and why cutting corners on sleep undermines our physical health.
For the first time, scientists from the University of California, Berkeley (UC Berkeley) have discovered just why growth hormone (GH) surges at night, particularly in deep sleep – something we've known for a while but not the mechanism driving it. In this animal study, the team uncovered a novel feedback mechanism that balances hormone levels to power a range of tasks – including helping to build muscle.
“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. “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.”
GH isn’t just about children growing taller; in adults, it is crucial for maintaining muscle mass, bone density, healthy fat distribution and blood sugar regulation. Low levels are linked to frailty, weaker bones, belly fat, insulin resistance and higher cardiovascular risk – all hallmarks of aging. The link between sleep and GH is clear, but the precise neuroendocrine wiring that allows one to amplify the other wasn't.
Essentially, we have one set of neurons that releases growth hormone–releasing hormone (GHRH), which stimulates the pituitary to produce growth hormone. While another set releases somatostatin (SST), which inhibits it (this group is further divided into two subtypes that fine-tune the brake on GH output). In this study, the team focused on these two small peptide hormones, showing how together these cells act like an accelerator and a brake to balance GH release across different phases of sleep.
The team used genetic tools, calcium imaging and optogenetics to identify how these two gas pedal/brake hormones operate differently during REM and non-REM sleep. Somatostatin and GHRH spike during REM sleep to boost GH levels, but SST decreases and GHRH increases only moderately during non-REM sleep to boost GH.
If this sounds confusing to you, you're not alone. But the scientists discovered that although SST is described as an inhibitor, it can also act as a timekeeper. In REM sleep, bursts of both SST and GHRH combine to produce sharp pulses of GH, while in non-REM sleep, SST activity drops, allowing steadier hormone release. Together, the two systems ensure GH is delivered in the right rhythm at the right time.
The researchers also discovered a feedback loop between GH and a brainstem hub called the locus coeruleus, which functions to keep us alert. As GH builds up during sleep, it gently stimulates this hub to prepare the body for waking up. But if the locus coeruleus is overstimulated, it flips the other way and promotes sleepiness again. The result is a yin–yang balance, where sleep drives GH, and GH helps shape the rhythm of sleep and wakefulness.
Ultimately, what you need to know is that this rhythm, or pulses of GH that's released into the bloodstream during the night, primes the body’s tissues to rebuild.
“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,” said co-author Daniel Silverman, a postdoctoral fellow at a UC Berkeley. “Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health.”
So losing sleep isn’t just about feeling tired – it means missing out on the prime anabolic window the body depends on to repair and renew itself. Athletes who want to build muscle, older adults trying to preserve bone strength and people managing weight or blood sugar all depend on GH, and GH depends on sleep. Because GH naturally declines with age, protecting sleep may be one of the simplest ways we have to promote healthier aging.
“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 added.
While the discovery was made through studying mice, the same circuits exist in humans and the patterns of hormone release line up closely. And understanding how GH is regulated during the different stages of sleep means scientists now have different targets that could ultimately help fine-tune that rhythm that's crucial to restoration.
Previous studies have uncovered the many ways poor sleep contributes to advanced biological aging, and this new research adds yet more complexity to the processes that take place between our waking and sleeping states. The takeaway here is: If you're trying to build or maintain muscle mass, skipping sleep can have both short-term and long-term impacts on your body.
“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.”
The research was published in the journal Cell.
