Methionine potentiates both basal and GHRH-induced GH secretion in children.
OBJECTIVE
It is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF-1 > 100 micrograms/l).


METHODS
We studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 microgram/kg i.v. at 0 min)-induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over e0 min) (group D) on GH secretion was also studied.


METHODS
Thirty-four children (20 male and 14 female, age 12.8-14.0 years), divided into four groups.


METHODS
Serum Gh was measured in duplicate by immunoradiometric assay.


RESULTS
In group A, MET increased basal Gh levels (peak, mean +/- SEM 14.6 +/- 2.6 vs 2.6 +/- 0.6 mU/l; P < 0.01) and potentiated the GH response to 1 microgram/kg i.v. GHRH (78.0 +/- 17.6 vs 41.6 +/0 9.8 mU/I; P < 0.02). In group B, ARG (0.2 g/kg) increased basal GH levels (16.2 +/- 5.2 vs 2.4 +/- 0.6 mU/I; P < 0.03) and potentiated the GH response to GHRH (119.6 +/- 20.4 vs 48.8 +/- 14.2 mU/I; P < 0.01). In group C, ARG (0.5 g/kg) induced a clear GH rise (28.0 +/- 3.8 vs 2.0 +/- 0.6 mU/I; P < 0.001) and potentiated the GH response to GHRH (93.4 +/- 10.0 vs 34.2 +/- 4.6 mU/I; P < 0.001). The GH responses to MET and ARG alone in groups A and B were similar and lower than that to ARG in group C. The GH responses to MET or ARG combined with GHRH in groups A, B and C were similar. In group D MET failed to modify the GH response to 0.5 g/kg i.v. ARG (10.8 +/- 6.4 vs 9.6 +/- 6.0 mU/I).


CONCLUSIONS
Methionine potentiates both basal and GHRH-induced Gh secretion in children as effectively as arginine. As methionine has no interaction with arginine, our data suggest that these amino acids act via a common mechanism.
Bellone
J
J
Division of Endocrinology, University of Turin, Italy.
Farello
G
G
Bartolotta
E
E
Aimaretti
G
G
Bellone
S
S
Mucci
M
M
De Matteis
F
F
Ghigo
E
E
D000293:Adolescent; D001120:Arginine / Q000627:therapeutic use; D002648:Child; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D006801:Humans; D015592:Immunoradiometric Assay; D008297:Male; D008715:Methionine / Q000627:therapeutic use*
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D008715:Methionine