GROWTH-HORMONE STATUS DURING LONG-TERM HEXARELIN THERAPY

Hexarelin, a powerful GH-releasing peptide, is capable of causing prof ound GH release in normal subjects after oral, intranasal, iv, and sc administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 wee ks of twice-daily sc hexarelin therapy (1.5 mu g/kg BW) on the GH resp onse to a single injection of hexarelin, and also the GH response to h exarelin 4 weeks after cessation of hexarelin therapy. We have also as sessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formatio n (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-termina l propeptide of type I collagen), and resorption (urinary deoxypyridin oline and pyridinoline), body composition, and bone mineral density. T he mean (+/-SEM) area under the GH curve (AUC(GH)) at weeks 0, 1, 4, 1 6, and 20 were 19.1 +/- 2.4 mu g/L.h, 13.1 +/- 2.3 mu g/L.h, 12.3 +/- 2.4 mu g/L.h, 10.5 +/- 1.8 mu g/L.h, and 19.4 +/- 3.7 mu g/L.h, respec tively. There was a significant change in AUG(GH) over the study perio d (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUG,, at week 4 and Reek 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUG(GH) increased significantly, compared with AUC(GH) a t week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change signific antly over the 20-week period (P = 0.24 and P = 0.74, respectively). O f the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared w ith baseline (P = 0.019). Total body fat, lean body mass, and bone min eral density had not changed significantly at week 16, compared with b aseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the pre sent study, the biological impact of this hexarelin schedule on the GH -IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.