The negative GH auto-feedback in childhood: effects of rhGH and/or GHRH on the somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue, in children.
Bellone. J J; Bellone. S S; Aimaretti. G G; Valetto. M R MR; Baffoni. C C; Corneli. G G; Origlia. C C; Arvat. E E; Ghigo. E E
Key Findings
- A prior dose of GH markedly suppresses the GH spike that follows GHRH or hexarelin.
- Pre‑treating with GHRH does not diminish the subsequent GH response to another GHRH dose.
- The negative feedback appears to be mediated by somatostatin and is active in pre‑pubertal children.
Practical Outcomes
- For biohackers, the study suggests that taking exogenous GH may blunt the effectiveness of later GH‑secretagogue doses like hexarelin, so timing and dosing intervals could matter. However, because the research was done in children, the findings may not directly apply to adult protocols for longevity or performance.
Summary
In kids with normal short stature, giving growth hormone (GH) reduces the body's ability to release more GH when later stimulated with either a GH‑releasing hormone (GHRH) or a GH‑secretagogue called hexarelin. However, giving GHRH first does not blunt the next GH surge. This shows that a natural feedback loop (likely via somatostatin) already works in childhood, but the exact reason why GHRH doesn't shut itself down is still unknown.
Abstract
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 microg/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 microg/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 microg/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7+/-2.3 vs 38.8+/-4.5 microg/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 microg/l) was similar to that in group B and was not significantly modified by pre-treatment with rhGH+ GHRH (6.9+/-2.7 microg/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 microg/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 auto-feedback is already operative in childhood; the reason why the GHRH- induced GH rise is not inhibited by GHRH pre-treatment is unexplained.
Study Information
pubmed
2000
10.1007/bf03343699