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.

We test the interlinked hypotheses that in healthy older adults: 1). i.v. injection of GH-releasing peptide-2 (GHRP-2) and GHRH synergizes more in aging women than men; 2). sc infusion of both GHRP-2 (1 microg/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 <or= 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 IGFBP-3 (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.