The somatotropic axis and sleep.

We review the evidence suggesting that hypothalamic growth hormone (GH)-releasing hormone (GHRH) stimulates sleep and growth hormone secretion simultaneously. GHRH injected into the cerebral ventricles, systemic circulation or the preoptic region enhances non-REM sleep (NREMS) in rats, rabbits and mice, and GHRH administered systemically promotes NREMS in humans. GHRH may also stimulate REMS but this effect is indirect and requires the presence of GH. Inhibition of endogenous GHRH (antibodies, antagonist, somatostatin, high doses of GH or IGF-1) suppresses both NREMS and GH secretion. Mutant rats and mice with deficiencies of GHRH signaling, and transgenic mice with decreased GHRH production sleep less than normal animals. Hypothalamic GHRH mRNA and GHRH content display diurnal variations and change in response to sleep deprivation. The NREMS-promoting activity of GHRH is independent of GH and is mediated by the preoptic region. It is suggested that promotion of NREMS and stimulation of GH are parallel outputs of hypothalamic GHRH through which anabolic activities in the body are are synchronized to periods of sleep.