GH responsiveness to repeated GHRH or hexarelin administration in normal adults

GH responses, calculated as the net incremental area under the curve (GH nAUC/h), to two consecutive 1 microgram/kg/bw iv GHRH boluses (administered at 0 and 120 min, test a), to one 1 microgram/kg/bw iv GHRH bolus followed by a 1 microgram/kg/bw iv hexarelin bolus (administered at 0 and 120 min respectively, test b) and to two consecutive 1 microgram/kg/bw iv hexarelin boluses (administered at 0 and 120 min, test c) were evaluated in 6 normal adults. The first GHRH injection caused a clear rise in serum GH levels in all subjects (mean GH nAUC/h, test a: 832.1 +/- 59.4 ng/ml/h, range: 723.7-1074.0 ng/ml/h; test b: 859.2 +/- 122.9 ng/ml/h, range 618.0-1422.7 ng/ml/h). Hexarelin administration elicited a marked GH release (test c: 1424 +/- 208.2 ng/ml/h, range: 810.0-2154.0 ng/ml/h), which was significantly higher than those observed after GHRH (vs test a: p < 0.02, vs test b: p < 0.05). After the first GHRH bolus, the second GHRH injection (test a) was unable to sustain GH elevated levels (mean GH nAUC: 74.5 +/- 26.5 ng/ml/h, range: 9.7-182.2 ng/ml/h), while hexarelin administration (test b) caused a clear GH rise in all subjects (GH nAUC: 1049.7 +/- 105.2 ng/ml/h, range: 786.0-1356.0 ng/ml/h). Repeated hexarelin administration (test c) was associated with a significant (p < 0.02) reduction of GH responses to the second bolus (286.6 +/- 43.1 ng/ml/h), which were however significantly higher than those observed after the second GHRH bolus (p < 0.05). In conclusion, these results demonstrate that repeated hexarelin administration causes a reduction of GH responsiveness, which is less marked than that induced by repeated GHRH administration, probably due to the more potent GH-releasing effect of hexarelin. Moreover, when administered after GHRH, hexarelin has a sustained GH-releasing effect in contrast to the poor efficacy of GHRH, thus suggesting that the acute effect of hexarelin is probably not mediated through hypothalamic GHRH pathways.