Low doses of either intravenously or orally administered arginine are able 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 this 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 and 5 g ARG(group A, B and C, respectively) as well as oral administration of 8 g ARG(group D) on the GH response to 1 microgram/kg i.v.GHRH in 27 healthy elderly subjects (11 M and 16 F, age 70-86 yr, BMI 21-25 kg/m2). In group A (n = 7) 30 g i.v. ARG strikingly enhanced the GHRH-induced GH rise (peak, mean +/- SE: 41.5 +/- 4.4 vs 11.7 +/- 5.3 micrograms/L, p < 0.05). Similarly, in group B (n = 6) and D (n = 7) 10 g i.v. and 8 g oral ARG enhanced the GH response to GHRH (20.9 +/- 4.7 vs 8.3 +/- 2.8 micrograms/L, p < 0.03 and 31.0 +/- 5.3 vs 11.4 +/- 3.4 micrograms/L, p < 0.03, respectively). In contrast, in group C (n = 7) 5 g i.v. ARG failed to modify the GHRH-induced GH rise (6.0 +/- 1.6 vs 3.5 +/- 0.9 micrograms/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 greater than the GH response in group C. These results show that the GH response to GHRH in elderly subjects is enhanced even by low iv doses of arginine and by the orally administered amino acid, the lowest effective dose being 8 g. Moreover, they imply that the combined administration of GHRH and arginine may be a useful approach to restore the impaired function of the GH-IGF axis in aging.
Ghigo
E
E
Dipartimento di Fisiopatologia Clinica, Università di Torino, Italy.
Ceda
G P
GP
Valcavi
R
R
Goffi
S
S
Zini
M
M
Mucci
M
M
Valenti
G
G
Cocchi
D
D
Müller
E E
EE
Camanni
F
F
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D001120:Arginine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine