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Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging

Ghigo E, Arvat E, Rizzi G, Goffi S, Grottoli S, Mucci M, Boghen MF, Camanni F. Growth hormonereleasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging. Eur J Endocrinol 1994;131:499–503. ISSN 0804–4643

The reduced activity of the growth hormone (GH)–insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65–82 years) were studied. The effect of oral administration of 300 µg/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 µg/kg iv) also was studied. Before treatment, oral administration of 300 µg/kg GHRP-6 elicited a clear GH rise (peak 10.7 ± 3.3 µg/l; AUC 353.1 ± 90.6 µg·l^–1·h^–1). which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 ± 1.5 µg/l; AUC 106.5 ±43.9 µg · l^–1·h^–1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 ± 2.9 µg/l; AUC 499.8 ± 107.2 µg·l^–1·h^–1). The IGF-I levels were not increased significantly after treatment (77.1 ± 8.4 vs 84.1 ± 12.2 µg/l). In conclusion, our results demonstrate that, in aging, oral GHRP-6 administration elicits a GH response that is higher than the maximal effective dose of intravenous GHRH and that the effect of the hexapeptide does not vanish after short-term treatment. More prolonged treatment and/or more frequent administrations of GHRP-6 are likely needed to increase IGF-I levels.

F Camanni, Division of Endocrinology, Department of Pathophysiology, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy

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