GROWTH HORMONE-RELEASING EFFECT OF ORAL GROWTH-HORMONE-RELEASING-PEPTIDE-6 (GHRP-6) ADMINISTRATION IN CHILDREN WITH SHORT STATURE

Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its ac tivity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of o ral GHRP-6 (300 mu g/kg) was compared with that of the maximally effec tive dose of intravenous GH-releasing hormone (GHRH-29, 1 mu g/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG) , even when administered by oral route at low dose (4 g), we studied a lso the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal st age I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I > 70 mu g/l). In a first group of children (N = 7), oral GHRP -6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 mu g/l, p<0.0006; area under curve: 1527.3 +/- 263.9 mu g/l(-1) h(-1)) which was similar to that el icited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0. 9 mu g/l, p < 0.007; area under curve: 1429.4 +/- 248.2 mu gl(-1) h(-1 )). In a second group of children (N = 6), the GH response to oral GHR P-6 administration (peak at 75 min vs baseline: 18.5 +/- 5.1 vs 1.5 +/ - 0.6 mu g/l, p < 0.01; area under curve: 1598.5 +/- 289.3 mu gl(-1) h (-1)) was not modified by co-administration of oral ARG (peak at 90 mi n vs baseline: 15.2 +/- 5.6 vs 0.9 +/- 0.3 mu g/l, p < 0.002; area und er curve: 1327.8 +/- 193.2 mu gl(-1) h(-1)). The amount of GK released and the timing of the somatotrope response after the oral administrat ion of GHRP-6 were similar in the two groups. In conclusion the presen t data show that in normal short children the oral administration of G HRP-6 is able to increase GH secretion to an extent similar to that ob served after intravenous administration of the maximally effective GHR H dose. Moreover, in contrast to GHRH, the effect of GHRP-6 is not enh anced by low-dose oral ARG. As this amino acid likely acts via inhibit ion of hypothalamic somatostatin release, our data suggest that a decr ease in the somatostatinergic activity does not improve the GH-releasi ng effect of GHRP-6 in childhood, at variance with that observed after GHRH. Our results suggest that GHRP-6 could be clinically useful to s timulate GH secretion in short children.