TY - JOUR
T1 - The negative GH auto-feedback in childhood
T2 - Effects of rhGH and/or GHRH on the somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue, in children
AU - Bellone, J.
AU - Bellone, S.
AU - Aimaretti, G.
AU - Valetto, M. R.
AU - Baffoni, C.
AU - Corneli, G.
AU - Origlia, C.
AU - Arvat, E.
AU - Ghigo, Ezio
N1 - Funding Information:
This study was supported by grants from Ministero Università Ricerca Scientifica e Tecnologica (grant no. 9706151106) Rome, Fondazione Studio Malattie Endocrino-Metaboliche (Turin), and Europeptides, Argenteuil, France. The authors thank Prof. F. Camanni and Dr. R. Deghenghi for their support to the study and Mrs. M. Talliano for her skilful technical assistance.
PY - 2000
Y1 - 2000
N2 - Aim of the present study was to further clarify the negative GH auto-feedback mechanisms in childhood. To this goal we studied the effects of rhGH and/or GHRH administration on the GH response to GHRH or hexarelin (HEX), a peptidyl GH secretagogue, in normal short children. In 34 prepubertal children (12 girls and 22 boys, age 8.2- 14.2 yr) with normal short stature (normal height velocity and IGF-I levels) the following tests were performed: group A (no.=11): GHRH (GHRH 1 - 29, Geref, Serono; 1 μg/kg iv at 150 min) preceded by saline or GHRH at 0 min; group B (no.=6): GHRH preceded by saline or rhGH (0.005 IU/kg iv at 0 min); group C (no.=6): GHRH preceded by rhGH alone or combined with GHRH; group D (no.=6): HEX (2 μg/kg iv at 150 min) alone or preceded by rhGH. In group A, the GH response to GHRH was not modified by pre-treatment with GHRH (GH peak, mean±SEM: 16.7±2.9 vs 15.1±2.3 μg/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7±2.3 vs 38.8±4.5 μg/l, p<0.001); the GH rise after rhGH in group B overlapped with that after GHRH in group A. In group C, the GH response to GHRH after pre-treatment with rhGH (13.2±4.0 μg/l) was similar to that in group B and was not significantly modified by pre-treatment with rhGH+ GHRH (6.9±2.7 μg/l); the GH rise after rhGH+GHRH was higher (p<0.05) than that after rhGH alone. In group D, the GH response to HEX was significantly blunted by pre-treatment with rhGH (34.1±11.7 vs 51.2±17.9 μg/l, p<0.05). Our results demonstrate that in childhood the somatotroph response to GHRH is preserved after GHRH while it is inhibited after rhGH administration, which is also able to blunt the GH response to HEX. Thus, the somatostatin-mediated negative GH autofeedback is already operative in childhood; the reason why the GHRH- induced GH rise is not inhibited by GHRH pre-treatment is unexplained. (C)2000, Editrice Kurtis.
AB - Aim of the present study was to further clarify the negative GH auto-feedback mechanisms in childhood. To this goal we studied the effects of rhGH and/or GHRH administration on the GH response to GHRH or hexarelin (HEX), a peptidyl GH secretagogue, in normal short children. In 34 prepubertal children (12 girls and 22 boys, age 8.2- 14.2 yr) with normal short stature (normal height velocity and IGF-I levels) the following tests were performed: group A (no.=11): GHRH (GHRH 1 - 29, Geref, Serono; 1 μg/kg iv at 150 min) preceded by saline or GHRH at 0 min; group B (no.=6): GHRH preceded by saline or rhGH (0.005 IU/kg iv at 0 min); group C (no.=6): GHRH preceded by rhGH alone or combined with GHRH; group D (no.=6): HEX (2 μg/kg iv at 150 min) alone or preceded by rhGH. In group A, the GH response to GHRH was not modified by pre-treatment with GHRH (GH peak, mean±SEM: 16.7±2.9 vs 15.1±2.3 μg/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7±2.3 vs 38.8±4.5 μg/l, p<0.001); the GH rise after rhGH in group B overlapped with that after GHRH in group A. In group C, the GH response to GHRH after pre-treatment with rhGH (13.2±4.0 μg/l) was similar to that in group B and was not significantly modified by pre-treatment with rhGH+ GHRH (6.9±2.7 μg/l); the GH rise after rhGH+GHRH was higher (p<0.05) than that after rhGH alone. In group D, the GH response to HEX was significantly blunted by pre-treatment with rhGH (34.1±11.7 vs 51.2±17.9 μg/l, p<0.05). Our results demonstrate that in childhood the somatotroph response to GHRH is preserved after GHRH while it is inhibited after rhGH administration, which is also able to blunt the GH response to HEX. Thus, the somatostatin-mediated negative GH autofeedback is already operative in childhood; the reason why the GHRH- induced GH rise is not inhibited by GHRH pre-treatment is unexplained. (C)2000, Editrice Kurtis.
KW - Childhood
KW - Feedback
KW - GHRH
KW - rhGH
UR - http://www.scopus.com/inward/record.url?scp=0034001981&partnerID=8YFLogxK
U2 - 10.1007/BF03343699
DO - 10.1007/BF03343699
M3 - Article
SN - 0391-4097
VL - 23
SP - 158
EP - 162
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
IS - 3
ER -
