Growth Hormone-Releasing Peptide-6 Stimulates Sleep, Growth Hormone, ACTH and Cortisol Release in Normal Man

Abstract

The synthetic hexapeptide growth hormone-releasing peptide (GHRP-6) stimulates growth hormone (GH) release in animals and man. GH-releasing hormone (GHRH) has the same effect. In addition, pulsatile administration of GHRH in normal men results in increased slow-wave sleep (SWS) and blunted cortisol levels. The effect of GHRP on nocturnal hormone secretion and on the sleep electroencephalogram (EEG) is still unknown. We compared the effect of repetitive i.v. boluses (4 × 50 µg) of GHRP and placebo (PL) on the sleep EEG (23.00 to 07.00 h) and on the secretion profiles of GH, ACTH and cortisol (20.00 to 07.00 h) in normal male controls. After GHRP, the GH concentration (22.00 to 03.00 h) increased (15.4 ± 9.6 ng/ml after GHRP vs. 5.5 ± 4.0 ng/ml after PL, p < 0.02), as did the ACTH level (22.00 to 02.00 h: 21.0 ± 5.3 pg/ml after GHRP vs. 16.6 ± 3.1 pg/ml after PL, 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 GHRP vs. 25.2 ± 9.0 ng/ml after PL, p < 0.02). Stage 2 sleep increased (270.1 ± 25.3 min after GHRP vs. 245.4 ± 25.8 min after PL, p < 0.02), whereas other sleep-EEG variables including SWS remained unchanged. Our data demonstrate that GHRP stimulates not only GH release but also hypothalamic-pituitary-adrenocortical hormone secretion. The latter effect is opposite to the blunting of cortisol after GHRH. Both GHRP and GHRH promote sleep. However, GHRP enhances stage 2 sleep and does not affect SWS. The different actions of GHRP and GHRH are a further indication that they act at different receptors.