Growth hormone responses during strenuous exercise: the role of GH-releasing hormone and GH-releasing peptide-2

Purpose and Methods: This study was designed to investigate the role of two effective releasers of growth hormone (GH): GHRH and GHRP-2 during exercis e (EX). Eight healthy male subjects (ages: 22 +/- 1.2 (mean +/- SD) yr, BMI : 22.5 +/- 2.2 kg.m(-2)) were exposed to maximally stimulating dose of 100 mu g GHRH iv, and 200 mu g GHRP-2 iv, during incremental EX on a cycle ergo meter to exhaustion. GH responses after EX alone were compared with the res ponses 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 fa sted state at intervals for 2 h postexercise and the area under the GH resp onse curve (AUC) was calculated by trapezoidal integration. Results: Signif icant differences (P < 0.003) were observed between the AUCs after administ ration of EX alone (mean +/- SEM): 7324 +/- 312 mu g.L-1.120 min, after EX plus GHRH: 6952 +/- 1083, after EX plus GHRP-2: 14674 +/- 2210, and after t he combination EX plus GHRH plus GHRP-2: 17673 +/- 1670. However, AUCs afte r each combination did not differ significantly from those after arithmetic al addition of each separate stimulus, indicating that the mechanisms of th e 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. R-2) of the GH response to the comb ination 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 pot entiate 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 respon se, a synergistic action of GHRP-2 on GHRH could be observed. Conclusions: The data indicate that under strenuous EX conditions, endogenous GHRH activ ity causes a further increase of GH release. A GHRP-2 mediated mechanism in the central neuroendocrine regulation acts as a "booster," possibly by sti mulating the effects of GHRH and/or an unknown hypothalamic factor, as well as by stimulating the pituitary GH release directly.