LOW-DOSES OF EITHER INTRAVENOUSLY OR ORALLY-ADMINISTERED ARGININE AREABLE TO ENHANCE GROWTH-HORMONE RESPONSE TO GROWTH-HORMONE RELEASING HORMONE IN ELDERLY SUBJECTS

Reportedly, the responsiveness of somatotrope cells to GHRH is reduced in elderly humans but it is totally restored by arginine (ARG) which likely acts by inhibiting hypothalamic release of somatostatin. As thi s effect was observed after infusion of high doses of the amino acid, in this study, we compared the effect of iv administration of 30,10 an d 5 g ARG(group A,B and C, respectively) as well as oral administratio n of 8 g ARG(group D) on the GH response to 1 mu g/kg iv GHRH in 27 he althy elderly subjects (11 M and 16 F, age 70-86 yr, BMI 21-25 kg/m(2) ). In group A (n=7) 30 g iv ARG strikingly enhanced the GHRH-induced G H rise (peak, mean+/-SE: 41.5+/-4.4 vs 11.7+/-5.3 mu g/L, p<0.05). Sim ilarly, in group B (n=6) and D (n=7) 10 g iv and 8 g oral ARG enhanced the GH response to GHRH (20.9+/-4.7 vs 8.3+/-2.8 mu g/L, p<0.03 and 3 1.0+/-5.3 vs 11.4+/-3.4 mu g/t, p<0.03, respectively); In contrast, in group C (n=7) 5 g iv ARG failed to modify the GHRH-induced GH rise (6 .0+/-1.6 vs 3.5+/-0.9 mu g/L), The GH responses to GHRH alone did not significantly differ amongst groups; the GH responses-to GHRH and ARG were not significantly different among groups A, B and D and were grea ter than the GH response in group C. These results show that the GH re sponse to GHRH in elderly subjects is enhanced even by low iv doses of arginine and by the orally administered amino acid, the lowest effect ive dose being 8 g. Moreover, they imply that the combined administrat ion of GHRH and arginine may be a useful approach to restore the impai red function of the GH-IGF axis in aging.