Galanin infusion restores the blunted GH responses to GHRH administration during GH treatment in children with constitutional growth delay.

GH responses to GHRH (in basal conditions), GHRH (after six months of recombinant GH therapy) and GHRH plus galanin administration (after GH therapy) were determined in six children with constitutional growth delay (CGD). Before treatment, GHRH administration caused a clear rise of GH levels (mean GH peak: 38.0 +/- 7.2 ng/ml); mean GH net incremental area under the curve/120 min (GH nAUC) was 2631.0 +/- 519.8 ng/ml/120 min. During GH treatment, both height velocity and IGF-I levels significantly increased from 4.3 +/- 0.1 cm/yr to 9.4 +/- 0.9 cm/yr (p < 0.001) and from 218.7 +/- 12.3 ng/ml to 328.0 +/- 28.2 ng/ml (p < 0.001), respectively. After 6 months of GH therapy, mean GH peak (21.7 +/- 2.2 ng/ml) and mean GH nAUC (847.7 +/- 109.8 ng/ml/120 min) after GHRH administration were significantly lower (p < 0.05) than in basal conditions. Galanin infusion (10 micrograms/kg/bw) was able to completely restore the reduced GH responsiveness to GHRH administration. In fact, mean GH peak and mean GH nAUC after GHRH plus galanin were similar to those recorded after basal GHRH administration (GH peak: 37.5 +/- 4.0 ng/ml; GH nAUC: 2279.8 +/- 430.5 ng/ml/120 min). In conclusion, this study shows that the reduction of pituitary responsiveness to GHRH administration during GH treatment is not dependent on the depletion of the promptly GH releasable pool, since somatotroph refractoriness to GHRH can be overriden by the concomitant administration of galanin.