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UC Berkeley Study Maps Sleep Circuit That Drives Growth Hormone—and Signals the Brain to Wake

Mouse experiments published in Cell reveal growth hormone’s feedback on locus coeruleus neurons that gate arousal.

During sleep, the brain produces growth hormone to help build muscle and bone and reduce fat. UC Berkeley research in mice reveals the brain circuits that regulate growth hormone release, along with a brainstem feedback mechanism that promotes wakefulness after a good night's sleep.
Scientists track how growth hormone reinforces our muscles and bones while we're asleep
Sleep is known to promote tissue growth and regulate metabolism, partly by enhancing growth hormone (GH) release, but the underlying circuit mechanism is unknown. Ding et al. demonstrate how GH release, which is enhanced during both rapid eye movement (REM) and non-REM (NREM) sleep, is regulated by sleep-wake-dependent activity of distinct hypothalamic neurons expressing GH-releasing hormone (GHRH) and somatostatin (SST). SST neurons in the arcuate nucleus suppress GH release by inhibiting nearby GHRH neurons that stimulate GH release, whereas periventricular SST neurons inhibit GH release by projecting to the median eminence. GH release is associated with strong surges of both GHRH and SST activity during REM sleep but moderately increased GHRH and decreased SST activity during NREM sleep. Furthermore, Ding et al. identified a negative feedback pathway in which GH enhances the excitability of locus coeruleus neurons and increases wakefulness. Image credit: Ding et al., doi: 10.1016/j.cell.2025.05.039.

Overview

  • Researchers identified opposing hypothalamic neuron populations—GHRH to stimulate and somatostatin to inhibit—that shape growth hormone pulses differently during REM and non-REM sleep.
  • Optogenetics, chemogenetics, calcium imaging, and electrophysiology in mice showed that the sleep state strongly amplifies growth hormone release in response to the same neural inputs.
  • Growth hormone increased the excitability of wake-promoting locus coeruleus neurons, and removing growth hormone receptors there eliminated this arousal effect, while hormone infusion boosted alertness only with intact receptors.
  • The results outline a circuit that links sleep architecture with growth, metabolic control, and morning alertness, with therapeutic possibilities that remain to be tested beyond young adult mice.
  • The study, led by first author Xinlu Ding in Yang Dan’s UC Berkeley lab with Stanford collaborators, was funded by HHMI and the Pivotal Life Sciences Chancellor’s Chair fund and appears in Cell on September 4, 2025.