Mouse study maps sleep circuit tied to growth hormone release
UC Berkeley researchers found a brain feedback loop linking sleep, growth hormone and wakefulness, with possible implications for metabolism and brain disorders.
By Tom Brennan · Health & Medicine Correspondent
3 min read
UC Berkeley researchers have identified a brain circuit in mice that links sleep to the release of growth hormone, a hormone involved in growth, tissue repair and metabolism. The findings matter because the team says the circuit may help explain why poor sleep can disrupt growth, muscle repair, fat processing and brain function.
The study, published in Cell, traces the process to nerve cells in the hypothalamus and a feedback pathway involving the locus coeruleus, a brainstem region associated with alertness and attention. UC Berkeley said the work gives researchers a more detailed map of how sleep and hormone regulation affect each other.
Scientists have known that growth hormone rises during sleep, especially during deep non-REM sleep, according to UC Berkeley. What had been less clear was how the brain controls that release and how the hormone then acts back on the brain.
Xinlu Ding, first author of the study and a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute, said earlier understanding came largely from blood measurements taken during sleep. In the new work, Ding said, the researchers directly recorded neural activity in mice.
How the circuit works
The team studied mice in the lab of Yang Dan, a UC Berkeley professor of neuroscience and molecular and cell biology. Researchers placed electrodes in the animals' brains, used light to stimulate hypothalamic neurons and recorded neural activity across repeated sleep and wake periods.
UC Berkeley said the short sleep cycles of mice allowed the researchers to observe many shifts in growth hormone activity. The team focused on growth hormone-releasing hormone neurons and two types of somatostatin neurons, all located in the hypothalamus.
The study found that growth hormone-releasing hormone promotes growth hormone release, while somatostatin suppresses it. UC Berkeley said these signals changed depending on sleep stage: during REM sleep, both growth hormone-releasing hormone and somatostatin increased, while during non-REM sleep somatostatin fell and growth hormone-releasing hormone rose more moderately.
The researchers also reported that released growth hormone activates neurons in the locus coeruleus. UC Berkeley said that region helps control alertness, attention, thinking and responses to new experiences, and has been linked in other work to neurological and psychiatric disorders.
A feedback link to wakefulness
The newly described feedback loop suggests that growth hormone does more than rise during sleep, according to the researchers. As the hormone builds up, it can stimulate the locus coeruleus and promote wakefulness, the team reported.
Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author, said the work points to a balanced system in which sleep drives growth hormone release and the hormone feeds back to regulate wakefulness. He said the balance is tied to growth, repair and metabolic health.
UC Berkeley said the findings could eventually guide research into therapies for sleep disorders connected with metabolic diseases such as diabetes and with neurodegenerative conditions including Parkinson's and Alzheimer's disease. Silverman said the circuit may provide a new way to study whether the excitability of the locus coeruleus can be adjusted.
Ding said growth hormone may also have cognitive benefits by supporting arousal after waking, in addition to its roles in muscle, bone and fat tissue. The research was supported by the Howard Hughes Medical Institute and the Pivotal Life Sciences Chancellor's Chair fund, according to UC Berkeley.
This story draws on original reporting from ScienceDaily.