Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects
E Arvat, L Gianotti, S Grottoli, BP Imbimbo, V Lenaerts, R Deghenghi, F Camanni and E Ghigo
Department of Clinical Pathophysiology, University of Turin, Italy.
Although both spontaneous and stimulated GH secretion undergo an age-
related decline, the secretory capacity of somatotrope cells is preserved
in human aging. In the present study we compared the GH responses to
hexarelin, GHRH, and the combined administration of hexarelin and GHRH or
arginine in young and elderly subjects. Thirteen young (24- to 30-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) received the following as
single iv injections during 3 different treatment sessions: hexarelin (2
micrograms/kg), GHRH (2 micrograms/kg), or hexarelin (2 micrograms/kg) plus
GHRH (2 micrograms/kg). The second group (6 young and 8 elderly subjects)
was administered single iv injections of hexarelin (2 micrograms/kg) or
hexarelin (2 micrograms/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
micrograms/L; P < 0.001). In the first group the GH response to
hexarelin was greater in young compared to elderly subjects (area under the
curve from 0-120 = 4849 +/- 601 vs. 2112 +/- 683 micrograms.min/L; P <
0.001). GHRH elicited a lower GH response than that induced by hexarelin in
both young (1455 +/- 102 micrograms/h.L; P < 0.02) and elderly subjects
(563 +/- 87 micrograms/min.L; P < 0.02). GHRH potentiated the
somatotrope response to hexarelin in both young (7725 +/- 503
micrograms/min.L; P < 0.02) and elderly subjects (3895 +/- 612
micrograms/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 elderly subjects (4819 +/- 668 vs.
1649 +/- 459 micrograms/min.L; P < 0.001). The GH response to hexarelin
was potentiated by arginine in elderly (4139 +/- 1057 micrograms/min. L; P
< 0.001), but not in young subjects (4743 +/- 774 micrograms/min.L).
This study shows that the maximal effective dose of hexarelin releases more
GH than the maximal effective dose of GHRH in both normal young and elderly
subjects. The effect of hexarelin on GH secretion is age dependent, and the
GH response to the combined administration of hexarelin and GHRH was
significantly higher in young subjects compared to elderly subjects.
Arginine does not potentiate the GH response to hexarelin in young
subjects, whereas it significantly enhances it in elderly
subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
This article has been cited by other articles:
S. V Haijma, P S. van Dam, W. R de Vries, I. Maitimu-Smeele, C. Dieguez, F. F Casanueva, and H. P F Koppeschaar The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men
Eur. J. Endocrinol.,
April 1, 2005;
152(4):
575 - 580.
[Abstract][Full Text][PDF]
D. Erickson, D. M. Keenan, K. Mielke, K. Bradford, C. Y. Bowers, J. M. Miles, and J. D. Veldhuis Dual Secretagogue Drive of Burst-Like Growth Hormone Secretion in Postmenopausal Compared with Premenopausal Women Studied under an Experimental Estradiol Clamp
J. Clin. Endocrinol. Metab.,
September 1, 2004;
89(9):
4746 - 4754.
[Abstract][Full Text][PDF]
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev.,
June 1, 2004;
25(3):
426 - 457.
[Abstract][Full Text][PDF]
S. Nakamura, M. Mizuno, H. Katakami, A. C. Gore, and E. Terasawa Aging-Related Changes in in Vivo Release of Growth Hormone-Releasing Hormone and Somatostatin from the Stalk-Median Eminence in Female Rhesus Monkeys (Macaca mulatta)
J. Clin. Endocrinol. Metab.,
February 1, 2003;
88(2):
827 - 833.
[Abstract][Full Text][PDF]
M. J. Woller, G. Everson-Binotto, E. Nichols, A. Acheson, K. L. Keen, C. Y. Bowers, and E. Terasawa Aging-Related Changes in Release of Growth Hormone and Luteinizing Hormone in Female Rhesus Monkeys
J. Clin. Endocrinol. Metab.,
November 1, 2002;
87(11):
5160 - 5167.
[Abstract][Full Text][PDF]
M. Imazio, M. Bobbio, F. Broglio, A. Benso, V. Podio, M.R. Valetto, G. Bisi, E. Ghigo, and G.P. Trevi GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy
Eur J Heart Fail,
March 1, 2002;
4(2):
185 - 191.
[Abstract][Full Text][PDF]
P. Sytze van Dam, H. E. C. Smid, W. R. de Vries, M. Niesink, E. Bolscher, E. J. Waasdorp, C. Dieguez, F. F. Casanueva, and H. P. F. Koppeschaar Reduction of Free Fatty Acids By Acipimox Enhances the Growth Hormone (GH) Responses to GH-Releasing Peptide 2 in Elderly Men
J. Clin. Endocrinol. Metab.,
December 1, 2000;
85(12):
4706 - 4711.
[Abstract][Full Text]
R. C. Jenkins, A. Meguid El Nahas, M. E. Wilkie, C. B. Brown, J. Jones, E. Ghigo, and R. J. M. Ross The Effects of Dose, Nutrition, and Age on Hexarelin-Induced Anterior Pituitary Hormone Secretion in Adult Patients on Maintenance Hemodialysis
J. Clin. Endocrinol. Metab.,
April 1, 1999;
84(4):
1220 - 1225.
[Abstract][Full Text]
A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human
Endocr. Rev.,
December 1, 1998;
19(6):
717 - 797.
[Abstract][Full Text]
H. G. Maheshwari, S. S. Pezzoli, A. Rahim, S. M. Shalet, M. O. Thorner, and G. Baumann Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance
Am J Physiol Endocrinol Metab,
April 1, 2002;
282(4):
E943 - E951.
[Abstract][Full Text][PDF]
