2.50
Hdl Handle:
http://hdl.handle.net/10541/91678
Title:
Growth hormone status during long-term hexarelin therapy.
Authors:
Rahim, Asad; O'Neill, Paul A; Shalet, Stephen M
Abstract:
Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, i.v., and s.c. administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin therapy (1.5 micrograms/kg BW) on the GH response to a single injection of hexarelin, and also the GH response to hexarelin 4 weeks after cessation of hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-terminal propeptide of type I collagen), and resorption (urinary deoxypyridinoline and pyridinoline), body composition, and bone mineral density. The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20 were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4 micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUCGH increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74, respectively). Of the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared with baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density had not changed significantly at week 16, compared with baseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.
Affiliation:
Department of Endocrinology, Christie Hospital, Withington, Manchester, United Kingdom.
Citation:
Growth hormone status during long-term hexarelin therapy. 1998, 83 (5):1644-9 J. Clin. Endocrinol. Metab.
Journal:
Journal of Clinical Endocrinology and Metabolism
Issue Date:
May-1998
URI:
http://hdl.handle.net/10541/91678
PubMed ID:
9589671
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRahim, Asaden
dc.contributor.authorO'Neill, Paul Aen
dc.contributor.authorShalet, Stephen Men
dc.date.accessioned2010-02-09T17:03:26Z-
dc.date.available2010-02-09T17:03:26Z-
dc.date.issued1998-05-
dc.identifier.citationGrowth hormone status during long-term hexarelin therapy. 1998, 83 (5):1644-9 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid9589671-
dc.identifier.urihttp://hdl.handle.net/10541/91678-
dc.description.abstractHexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, i.v., and s.c. administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin therapy (1.5 micrograms/kg BW) on the GH response to a single injection of hexarelin, and also the GH response to hexarelin 4 weeks after cessation of hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-terminal propeptide of type I collagen), and resorption (urinary deoxypyridinoline and pyridinoline), body composition, and bone mineral density. The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20 were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4 micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUCGH increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74, respectively). Of the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared with baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density had not changed significantly at week 16, compared with baseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.en
dc.language.isoenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAmino Acids-
dc.subject.meshBody Composition-
dc.subject.meshBone Density-
dc.subject.meshFemale-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 3-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshOligopeptides-
dc.subject.meshOsteocalcin-
dc.subject.meshPeptide Fragments-
dc.subject.meshProcollagen-
dc.titleGrowth hormone status during long-term hexarelin therapy.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Withington, Manchester, United Kingdom.en
dc.identifier.journalJournal of Clinical Endocrinology and Metabolismen

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