GROWTH HORMONE-RELEASING PEPTIDE-6 STIMULATES SLEEP, GROWTH-HORMONE, ACTH AND CORTISOL RELEASE IN NORMAL MAN

The synthetic hexapeptide growth hormone-releasing peptide (GHRP-6) st imulates growth hormone (GH) release in animals and man. GH-releasing hormone (GHRH) has the same effect. In addition, pulsatile administrat ion of GHRH in normal men results in increased slow-wave sleep (SWS) a nd blunted cortisol levels. The effect of GHRP on nocturnal hormone se cretion and on the sleep electroencephalogram (EEG) is still unknown. We compared the effect of repetitive i.v. boluses (4 x 50 mu g) of GHR P and placebo (PL) on the sleep EEG (23.00 to 07.00 h) and on the secr etion profiles of GH, ACTH and cortisol (20.00 to 07.00 h) in normal m ale controls. After GHRP, the GH concentration (22.00 to 03.00 h) incr eased(15.4 +/- 9.6 ng/ml after GHRP vs. 5.5 +/- 4.0 ng/ml after FL, p < 0.02), as did the ACTH level (22.00 to 02.00 h: 21.0 +/- 5.3 pg/ml a fter GHRP vs. 16.6 +/- 3.1 pg/ml after FL, p < 0.02). During the total night, and particularly during the first half of the night, cortisol secretion was enhanced (22.00 to 03.00 h: 56.0 +/- 31.0 ng/ml after GH RP vs. 25.2 +/- 9.0 ng/ml after FL, p < 0.02). Stage 2 sleep increased (270.1 +/- 25.3 min after GHRP vs. 245.4 +/- 25.8 min after FL, p < 0 .02), whereas other sleep-EEG variables including SWS remained unchang ed. Our data demonstrate that GHRP stimulates not only GH release but also hypothalamic-pituitary-adrenocortical hormone secretion. The latt er effect is opposite to the blunting of cortisol after GHRH. Both GHR P and GHRH promote sleep. However, GHRP enhances stage 2 sleep and doe s not affect SWS. The different actions of GHRP and GHRH are a further indication that they act at different receptors.