Purpose and methods: This study was designed to investigate the role of two effective releasers of growth hormone (GH): GHRH and GHRP-2 during exercise (EX). Eight healthy male subjects (ages: 22 +/- 1.2 (mean +/- SD) yr, BMI: 22.5 +/- 2.2 kg x m(-2)) were exposed to maximally stimulating dose of 100 microg GHRH iv, and 200 microg GHRP-2 iv, during incremental EX on a cycle ergometer to exhaustion. GH responses after EX alone were compared with the responses after the combined administration of the same EX plus GHRH, EX plus GHRP-2, and EX plus GHRH plus GHRP-2. Blood samples were obtained in the fasted state at intervals for 2 h postexercise and the area under the GH response curve (AUC) was calculated by trapezoidal integration.
Results: Significant differences (P < 0.003) were observed between the AUCs after administration of EX alone (mean +/- SEM): 2,324 +/- 312 microg x L(-1) 120 min, after EX plus GHRH: 6,952 +/- 1,083, after EX plus GHRP-2: 14,674 +/- 2,210, and after the combination EX plus GHRH plus GHRP-2: 17,673 +/- 1,670. However, AUCs after each combination did not differ significantly from those after arithmetical addition of each separate stimulus, indicating that the mechanisms of the respective stimuli do not interact. Linear regression analysis on mean GH responses between 20 and 30 min after the start of EX showed that EX alone and GHRH alone explain about 59% (adj. R2) of the GH response to the combination EX plus GHRH. The ratio of the respective regression coefficients (GHRH vs EX) was about 2:1 (instead of 1:1), indicating that EX seems to potentiate the activity of GHRH. GHRH alone and EX alone also explained about 74% of the response to the combination EX plus GHRP-2. In the latter response, a synergistic action of GHRP-2 on GHRH could be observed.
Conclusions: The data indicate that under strenuous EX conditions, endogenous GHRH activity causes a further increase of GH release. A GHRP-2 mediated mechanism in the central neuroendocrine regulation acts as a "booster," possibly by stimulating the effects of GHRH and/or an unknown hypothalamic factor, as well as by stimulating the pituitary GH release directly.