Sustained Elevation of Pulsatile Growth Hormone (GH) Secretion and Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-3 (IGFBP-3), and IGFBP-5 Concentrations during 30-Day Continuous Subcutaneous Infusion of GH-Releasing Peptide-2 in Older Men and Women

Cyril Y. Bowers, Ramona Granda, Subburaman Mohan, Jonathan Kuipers, David Baylink, Johannes D. Veldhuis

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

We test the interlinked hypotheses that in healthy older adults: 1) iv injection of GH-releasing peptide-2 (GHRP-2) and GHRH synergizes more in aging women than men; 2) se infusion of both GHRP-2 (1 μ/kg·h = 1) and GHRH (1, 3, or 10) for 24 h augments GH secretion more than either agonist alone; and 3) continuous sc delivery of GHRP-2 (1) for 30 d stimulates daily GH secretion and IGF-I, IGF-binding protein-3 (IGFBP-3), and IGFBP-5. Acute two-peptide synergy was 3-fold greater in young (n = 16) than older volunteers (n = 17; P < 0.025) and was 2.3-fold higher in elderly women than men (P < 0.025). The 24-h infusion of GHRP-2 (1) combined with GHRH (3 or 10) in men and with GHRH (10) in women drove GH secretion more than GHRH alone (P ≤ 0.024). In the entire cohort (n = 11), GHRP-2/GHRH (1/10) stimulated GH secretion more than either GHRP-2 (1; P = 0.021) or GHRH (10; P = 0.012). The 30-d delivery of GHRP-2 (1; n = 17 subjects): 1) stimulated pulsatile, rhythmic, and entropic GH secretion by more than 3-fold on d 1 and more than 1.8-fold on d 14 and 30 (each P < 0.001 vs. saline); 2) elevated IGF-I to a stable plateau on d 1, 14, and 30 (P < 0.025 vs. baseline); and 3) increased IGFBP4 (P < 0.01) and IGFBP-5 (P < 0.025) on d 14 and/or 30. Safety screening tests remained normal. In summary, in healthy elderly women and men: 1) acute synergy of GHRP-2 and GHRH is greater in the female; 2) 24-h combined GHRP-2 and GHRH drive is more effective than either agonist alone; and 3) 30-d stimulation with GHRP-2 sustains a physiologically activated somatotropic axis. We conclude that age, gender, stimulus duration, and secretagogue combination determine acute, intermediate, and extended responses of the somatotropic axis in the older adult.

Original languageEnglish (US)
Pages (from-to)2290-2300
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number5
DOIs
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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