Objective: Growth hormone (GH) secretion in middle and late adulthood declines with age. However, the precise mechanisms causing this impairment in GH release are unknown. His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose related and specific manner in several species, including man. In order to gain a further insight into disrupted GH secretion in late adulthood, we evaluated GH responses to GHRP-6 or GHRH, administered either alone or in combination, in healthy young and late adulthood groups of subjects.
Design: All subjects underwent three different tests carried out in random order and separated by at least one week. Tests were performed at 0900 h after an overnight fast. GHRH (100 micrograms), GHRP-6 (90 micrograms) either alone or in combination were administered as an i.v. bolus.
Subjects: Groups of healthy young (mean +/- SEM 22 +/- 1.1 years, n = 9) and older adult subjects (59.5 +/- 1.7 years, n = 9) were studied.
Measurements: Serum GH levels were measured by radioimmunoassay.
Results: In the group of young adult subjects the combined administration of GHRH and GHRP-6 elicited a greater GH increase than GHRH alone (F = 21.9, P < 0.001) or GHRP-6 alone (F = 6.2, P = 0.01). Similarly, the response to the combined stimuli was also greater than with GHRH alone (F = 21.8, P < 0.001) or GHRP-6 alone (F = 23.9, P < 0.001) in the late adulthood group of subjects. GH responses to GHRH were greater in younger than in older subjects (F = 3.45, P = 0.03). In contrast, GH responses to either GHRP-6 (F = 0.71, P = NS) or combined GHRH plus GHRP-6 administration (F = 0.68, P = NS) were not significantly different between the two groups.
Conclusions: These data show that GH responses to GHRP-6 are much greater than to GHRH in late adulthood. The marked increase of plasma GH levels observed after administration of GHRP-6 alone or in combination with GHRH indicates that impaired GH secretion in late adulthood is a functional and potentially reversible state.