ARGININE AND GROWTH HORMONE-RELEASING HORMONE RESTORE THE BLUNTED GROWTH HORMONE-RELEASING ACTIVITY OF HEXARELIN IN ELDERLY SUBJECTS

Although both spontaneous and stimulated GH secretion undergo an age-r elated decline, the secretory capacity of somatotrope cells is preserv ed in human aging. In the present study we compared the GH responses t o hexarelin, GHRH, and the combined administration of hexarelin and GH RH or arginine in young and elderly subjects. Thirteen young (24- to 3 0-yr-old) and 16 elderly (65- to 84-yr-old) normal males were divided into 2 groups. The first group (7 young and 8 elderly subjects) receiv ed the following as single iv injections during 3 different treatment sessions: hexarelin (2 mu g/kg), GHRH (2 mu g/kg), or hexarelin (2 mu g/kg) plus GHRH (2 mu g/kg). The second group (6 young and 8 elderly s ubjects) was administered single iv injections of hexarelin (2 mu g/kg ) or hexarelin (2 mu g/kg) plus arginine (0.5 g/kg) during 2 different treatment sessions. In both groups basal IGF-I levels in the elderly were lower than those in young subjects (114.5 +/- 18.7 vs. 211.5 +/- 19.1 mu g/L; P < 0.001). In the first group the GH response to hexarel in was greater in young compared to elderly subjects (area under the c urve from 0-120 = 4849 +/- 601 vs. 2112 +/- 683 mu g.min/L; P < 0.001) . GHRH elicited a lower GH response than that induced by hexarelin in both young (1455 +/- 102 mu g/h.L; P < 0.02) and elderly subjects (563 +/- 87 mu g/min.L; P < 0.02). GHRH potentiated the somatotrope respon se to hexarelin in both young (7725 +/- 503 mu g/min.L; P < 0.02) and elderly subjects (3895 +/- 612 mu g/min.L; P < 0.02), but to a lesser extent in the latter (P < 0.001). In the second group, the GH response induced by hexarelin was also higher in young subjects than in elderl y subjects (4819 +/- 668 vs. 1649,+/- 459 mu g/min.L; P < 0.001). The GH response to hexarelin was potentiated by arginine in elderly (4139 +/- 1057 mu g/min.L; P < 0.001), but not in young subjects (4743 +/- 7 74 mu g/min.L). This study shows that the maximal effective dose of he xarelin releases more GH than the maximal effective dose of GHRH in bo th normal young and elderly subjects. The effect of hexarelin on GH se cretion is age dependent, and the GH response to the combined administ ration of hexarelin and GHRH was significantly higher in young subject s compared to elderly subjects. Arginine does not potentiate the GH re sponse to hexarelin in young subjects, whereas it significantly enhanc es it in elderly subjects. These findings suggest that hexarelin acts, at least partially, independently from GHRH and/or somatostatin. Thes e results also support the presence of a somatostatinergic hyperactivi ty in aging, which is probably related to a concomitant reduction in t he activity of GHRH-secreting neurons.