Galanin infusion partially restores the blunted growth hormone responses to repeated growth hormone releasing hormone stimuli in normal adults

Abstract

In order to understand the role exerted by the endogenous somatostatinergic tone in the blunting of GH responsiveness to repeated GHRH administration, we evaluated GH responses to the second GHRH bolus during a simultaneous infusion of galanin, which has been reported to inhibit the endogenous somatostatin release. Seven normal adults (3M/4F, age range 19–28 yr), admitted to the study after giving informed consent, were tested on three occasions, with a) two consecutive 1 μg/kg iv GHRH boluses administered at 0 min and 120 min, b) one GHRH bolus at 0 min followed by an infusion of 10 μ/kg bw galanin (diluted in 40 ml 0.9% NaCI) between 100 min and 140 min and c) two consecutive GHRH boluses (same dose and temporization of administration of test a) associated with a galanin infusion from 100 min to 140 min. GH responses were evaluated as the net incremental area under the curve (GH nAUC/h); all data were expressed as mean±SE. GH responses to the first GHRH bolus were similar in the three tests (mean GH nAUC, test A 990±80, test B: 1006±112, test C: 1077±80 ng/ml/h). In test A the second GHRH bolus was unable to sustain GH elevated levels (mean GH nAUC: 32±12 ng/ml/h vs first GHRH: 990±80 ng/ml/h, p<0.0001). Similarly, in test B galanin infusion alone was unable to determine a clear GH rise (mean GH nAUC: −25±16 vs first GHRH: 1006±112 ng/ml/h, p<0.0001). In test C, the concomitant galanin infusion enhanced GH responsiveness to the second GHRH bolus (mean GH nAUC: 407±73 ng/ml/h vs GHRH alone: 32±12 ng/ml/h, p<0.005), GH responses being however lower than after the first GHRH administration (p<0.0001). In conclusion, our data show that simultaneous galanin infusion partially restores GH response to the second GHRH bolus in normal adults, thus indicating that the depletion of the intracellular GH pool can not completely account for the reduction of GH responsiveness.