Effects of growth hormone-releasing peptide-6 on the nocturnal secretion of GH, ACTH and cortisol and on the sleep EEG in man: role of routes of administration.

After repeated intravenous (i.v.) boluses of growth hormone-releasing peptide-6 (GHRP-6) we found recently increases of growth hormone (GH), corticotropin (ACTH) and cortisol levels and of the amount of stage 2 sleep. In clinical use, oral (p.o.), intranasal (i.n.) and sublingual (s.l.) routes of administration have advantages over i.v. administration. We compared the sleep-endocrine effects of 300 microg/kg of body weight (b.w.) GHRP-6 in enteric-coated capsules given p.o. at 21.00 h and of 30 microg/kg GHRP-6 i.n. or 30 microg/kg GHRP-6 sl. given at 22.45 h in normal young male controls with placebo conditions. After GHRP-6 p.o. secretion of GH, ACTH and cortisol remained unchanged. The only effect of GHRP-6 s.l. was a trend toward an increase in GH in the first half of the night. GHRP-6 i.n. prompted a significant increase in GH concentration during the total night and a trend toward an increase in ACTH secretion during the first half of the night, whereas cortisol secretion remained unchanged. Furthermore, after GHRP-6 i.n., sleep stage 2 increased in the second half of the night by trend, and spectral analysis of total night non-rapid eye movement (REM) sleep revealed a decrease of delta power by trend. In contrast sleep stage 2 decreased during the second half of the night after GHRP-6 p.o. Our data demonstrate that GHRP-6 is capable of modulating GH and ACTH secretion as well as sleep. However, the effects depend upon dosage, duration and route of administration.