Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging.
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 micrograms/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 microgram/kg i.v.) also was studied. Before treatment, oral administration of 300 micrograms/kg GHRP-6 elicited a clear GH rise (peak 10.7 +/- 3.3 micrograms/l; AUC 353.1 +/- 90.6 micrograms.l-1.h-1), which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 +/- 1.5 micrograms/l; AUC 106.5 +/- 43.9 micrograms.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 micrograms/l; AUC 499.8 +/- 107.2 micrograms.l-1.h-1). The IGF-I levels were not increased significantly after treatment (77.1 +/- 8.4 vs 84.1 +/- 12.2 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathophysiology, University of Turin, Italy.
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Ghigo
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Arvat
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Rizzi
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Goffi
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Grottoli
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Mucci
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Boghen
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Camanni
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001682:Biological Availability; D005260:Female; D013006:Growth Hormone / Q000187:drug effects / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013237:Stereoisomerism
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone