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 mu g/kg/bw iv GHRH boluses (administe red at 0 and 120 min, test a), to one 1 mu g/kg bw iv GHRH bolus follo wed by a 1 mu g/kg/bw iv hexarelin bolus (administered at 0 and 120 mi n, respectively, test b) and to two consecutive 1 mu g/kg/bw iv hexare lin 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, rang e 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 (mea n GH nAUC: 74.5+/-26.5 ng/ml/h, range: 9.7-182.2 ng/ml/h), while hexar elin administration (test b) caused a clear GH rise in all subjects (G H 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 af ter the second GHRH bolus (p<0.05). In conclusion, these results demon strate that repeated hexarelin administration causes a reduction of GH responsiveness, which is less marked than that induced by repeated GH RH administration, probably due to the more potent OH-releasing effect of hexarelin, Moreover, when administered after GHRH, hexarelin has a sustained GH-releasing effect in contrast to the poor efficacy of GHR H, thus suggesting that the acute effect of hexarelin is probably not mediated through hypothalamic GHRH pathways.