The negative GH auto-feedback in childhood: Effects of rhGH and/or GHRH onthe somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue,in children

Aim of the present study was to further clarify the negative GH auto-feedba ck 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 pe ptidyl GH secretagogue, in normal short children. In 34 prepubertal childre n (12 girls and 22 boys, age 8.2- 14.2 yr) with normal short stature (norma l height velocity and IGF-I levels) the following tests were performed: gro up A (no.=11): GHRH (GHRH 1 - 29, Geref, Serono; 1 mu g/kg iv at 150 min) p receded by saline or GHRH at 0 min; group B (no.=6): GHRH preceded by salin e 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 mu g/kg iv at 150 min ) alone or preceded by rhGH. In group A, the GH response to GHRH was not mo dified by pre-treatment with GHRH (GH peak, mean +/- SEM: 16.7 +/- 2.9 vs 1 5.1 +/- 2.3 mu g/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7 +/- 2.3 vs 38.8 +/- 4.5 mu g/l, p<0.001); th e 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 mu g/l) was similar to that in group B and was not significantly modi fied by pre-treatment with rhGH+ GHRH (6.9 +/- 2.7 mu g/l); the GH rise aft er rhGH+GHRH was higher (p<0.05) than that after rhGH alone. In group D, th e GH response to HEX was significantly blunted by pre-treatment with rhGH ( 34.1 +/- 11.7 vs 51.2 +/- 17.9 mu g/l, p<0.05). Our results demonstrate tha t in childhood the somatotroph response to GHRH is preserved after GHRH whi le it is inhibited after rhGH administration, which is also able to blunt t he GH response to HEX. Thus, the somatostatin-mediated negative GH autofeed back is already operative in childhood; the reason why the GHRH- induced GH rise is not inhibited by GHRH pre-treatment is unexplained. (J. Endocrinol . Invest. 23:158-162, 2000) (C) 2000, Editrice Kurtis.