Effects of thyrotropin-releasing hormone on sleep and sleep-related growth hormone release in normal subjects

Effects of TRH on sleep and sleep-related growth hormone (GH) release were examined in four normal volunteers. A bolus of 500 microgram of synthetic TRH was injected iv at the onset of sleep, followed by continuous iv infusion of 1000 microgram of TRH dissolved in saline for 3 h on two nights. Saline alone was infused on two control nights in each of these subjects. Polygraphic sleep records showed that TRH transiently interrupted sleep on both nights in all of the four subjects. The arousal phenomenon was observed from 80 to 151 min after the start of TRH administration until 20 to 212 min after the end of TRH infusion. The mean (+/-SE) percentage of awakening on the nights of TRH administration was significantly larger than on the control nights (36.4 +/- 1.9% vs. 1.3 +/- 0.8%, P less than 0.001). Plasma GH increased in close relationship to the initial appearance of slow wave sleep (SWS) within 40 min after sleep onset on both control nights in all four subjects. On nights of TRH administration, however, plasma GH levels during the initial 80 min of sleep were significantly lower (P less than 0.005) than on control nights, whereas SWS was demonstrated before the interruption of sleep. On nights when sleep was interrupted by forced wakefulness 1 h after sleep onset, plasma GH rose to levels comparable to those on control nights during early sleep periods in all subjects examined. These results suggest that TRH inhibits sleep and sleep-related GH release in normal subjects.