ARGININE ENHANCES THE GROWTH HORMONE-RELEASING ACTIVITY OF A SYNTHETIC HEXAPEPTIDE (GHRP-6) IN ELDERLY BUT NOT IN YOUNG SUBJECTS AFTER ORAL-ADMINISTRATION

In man the GH-releasing hexapeptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHR P-6) has been shown to be active even after oral administration. On th e other hand, it has been shown that arginine (ARG) totally restores t he reduced somatotropic responsiveness to GHRH observed in aging. Base d on the foregoing, in this study we verified the GH-releasing activit y of oral GHRP-6 (300 mug/kg) in normal aging and the possible enhanci ng effect of 8 g oral ARG on the GH-releasing effect of GHRP-6. Eight young (age 24-32 yr) and 8 elderly (age 66-85 yr) subjects were studie d. In all the GH response to GHRH (1 mug/kg iv) was also studied. Both IGF-I levels and the GH response to iv GHRH were lower in elderly tha n in young subjects (mean+/-SE, IGF-I: 65.1+/-9.1 vs 142.9+/-9.4 mug/L , p<0.0001; GH peak: 5.4+/-1.0 vs 13.6 +/- 0.8 mug/L, p<0.0001). Oral GHRP-6 administration induced a GH rise in elderly which was lower, th ough not significantly, than that in young subjects (GH peak: 9.9+/-2. 0 vs 16.2+/-5.4 mug/L). Oral ARG administration enhanced the GHRP-6-in duced GH rise in elderly (GH peak: 22.1+/-3.3 mug/L, p<0.01 vs GHRP-6 alone) while failed to modify it in young subjects (GH peak: 13.5+/-3. 4 mug/L). The GH response to oral ARG+GHRP-6 in elderly was higher tha n that to all stimuli in young adults (p<0.05). In conclusion, present results show that in humans oral GHRP-6 administration induces a clea r GH increase also in aging. The finding that ARG enhanced the activit y of GHRP-6 in elderly but not in young subjects suggests that ARG is able to enhance the somatotropic responsiveness to GHRP-6 only when so matostatinergic activity is increased, i.e. in aging. Treatment with o ral GHRP-6 alone or combined with low oral ARG may be hypothesized to restore GH secretion in aging.