Deep, restful sleep promotes the release of growth hormones, which help build strong muscles and bones and burn fat. Teenagers cannot reach their full height without sufficient growth hormones, which are produced through restful sleep. However, why a lack of sleep – especially the early, deep phase known as non-REM sleep – reduces the release of growth hormones has been a mystery until now.
Insufficient Sleep Increases the Risk of Obesity, Diabetes and Cardiovascular Disease
In a study published in the current issue of the journal Cell, researchers at the University of California, Berkeley, examine the brain circuitry that controls the release of growth hormone during sleep and report a novel feedback mechanism in the brain that keeps growth hormone levels finely balanced. The findings provide a guide to understanding the interactions between sleep and hormone regulation. The new feedback mechanism could open up new avenues for treating people with sleep disorders associated with metabolic diseases such as diabetes, as well as degenerative diseases such as Parkinson’s and Alzheimer’s.
“It is known that growth hormone secretion is closely related to sleep, but until now this could only be demonstrated by drawing blood and checking growth hormone levels during sleep,” said the study’s first author, Xinlu Ding, a postdoctoral fellow in the Department of Neuroscience and the Helen Wills Neuroscience Institute at UC Berkeley. “We directly record neuronal activity in mice to see what’s going on. This provides us with a basic circuit layout that can be used to develop different treatments in the future.” As growth hormones regulate glucose and fat metabolism, insufficient sleep can also increase the risk of obesity, diabetes and cardiovascular disease.
The Sleep-Wake Cycle
The neurons that control the release of growth hormone during the sleep-wake cycle – growth hormone-releasing hormone (GHRH) and two types of somatostatin neurons – are located deep in the hypothalamus, an ancient brain center that has been preserved in all mammals. Once released, growth hormone increases the activity of neurons in the locus coeruleus, an area in the brainstem responsible for arousal, attention, cognition and curiosity. Dysregulation of neurons in the locus coeruleus is involved in numerous psychiatric and neurological disorders.
“Understanding the neural circuitry for growth hormone release could ultimately lead to new hormone therapies that improve sleep quality or restore normal growth hormone balance,” said Daniel Silverman, a postdoctoral researcher at UC Berkeley and co-author of the study. There are some experimental gene therapies that target a specific cell type. This circuit could be a novel approach to reduce locus coeruleus excitability, which has not been discussed before.
The researchers, who work in the lab of Yang Dan, professor of neuroscience and molecular and cell biology, studied the neuroendocrine circuit by inserting electrodes into the brains of mice and measuring the changes in activity after stimulating neurons in the hypothalamus with light. Mice sleep during the day and at night in short intervals of several minutes each, which offers numerous opportunities to study the changes in growth hormone during the sleep-wake cycle. Using state-of-the-art circuit tracers, the team found that the two small peptide hormones that control the release of growth hormone in the brain – GHRH, which promotes release, and somatostatin, which inhibits release – act differently during REM and non-REM sleep. Somatostatin and GHRH increase strongly during REM sleep to promote growth hormone, but somatostatin decreases and GHRH increases only moderately during non-REM sleep to promote growth hormone.
Growth Hormone Also Has Cognitive Benefits
Released growth hormone regulates locus coeruleus activity as a feedback mechanism to create a homeostatic yin-yang effect. During sleep, growth hormone slowly accumulates to stimulate the locus coeruleus and promote wakefulness, the new study found. However, when the locus coeruleus is overstimulated, it paradoxically promotes sleepiness, Silverman showed in a study published 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 drive the brain toward wakefulness,” Silverman said. Sleep drives the release of growth hormone, and growth hormone works back to regulate wakefulness. This balance is essential for growth, repair and metabolic health.
Because growth hormone acts in part through the locus coeruleus, which controls the brain’s overall arousal during wakefulness, a proper balance could have a broader impact on alertness and thinking. According to the researchers, growth hormones not only help build muscle and bone and reduce fat tissue, but may also have cognitive benefits and promote overall arousal levels upon waking.