Researchers at UC Berkeley have uncovered the brain circuits that regulate growth hormone release during sleep, revealing a feedback mechanism that could pave the way for new treatments for sleep disorders and metabolic conditions.
A new study from the University of California, Berkeley, sheds light on how sleep influences growth hormone levels, providing crucial insights that could lead to treatments for sleep disorders and metabolic diseases.
The research, conducted on mice and published in the journal Cell, identifies the specific brain circuits that control the release of growth hormone during sleep. This hormone is vital for building muscle, strengthening bones and reducing fat.
“People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep,” first author Xinlu Ding, a postdoctoral fellow in UC Berkeley’s Department of Neuroscience and the Helen Wills Neuroscience Institute, said in a news release. “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 implications of this study are significant: it maps out how sleep and hormone regulation interact, revealing a novel feedback mechanism that keeps growth hormone levels balanced. This mechanism could open new avenues for treating sleep disorders linked to metabolic conditions such as diabetes and degenerative diseases like Parkinson’s and Alzheimer’s.
Neurons responsible for growth hormone release reside deep within the hypothalamus, an ancient brain region conserved across mammal species. These neurons include growth hormone-releasing hormone (GHRH) neurons and two types of somatostatin neurons.
Once growth hormone is released, it activates neurons in the locus coeruleus, a brainstem area tied to arousal, attention, cognition and novelty seeking.
“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,” added co-author Daniel Silverman, a UC Berkeley postdoctoral fellow. “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 study, carried out in the lab of Yang Dan, a professor of neuroscience and of molecular and cell biology, utilized state-of-the-art circuit tracing techniques. The researchers inserted electrodes in mice brains to measure neural activity changes after light-stimulated neuron activation.
Their findings revealed that somatostatin and GHRH hormones operate differently during REM and non-REM sleep. During REM sleep, both hormones surge to boost growth hormone levels. However, during non-REM sleep, somatostatin decreases while GHRH moderately increases, maintaining the hormone’s release.
“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 added. “Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health.”
In addition to its metabolic benefits, growth hormone may also enhance cognitive function, promoting overall arousal levels when waking up.
“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,” added Ding.