ACUTE ADMINISTRATION OF RECOMBINANT HUMAN GROWTH-HORMONE INHIBITS THESOMATOTROPE RESPONSIVENESS TO GROWTH HORMONE-RELEASING HORMONE IN CHILDHOOD

In adulthood the growth hormone (GH) response to growth hormone-releas ing hormone (GHRH) is inhibited by previous acute administration of ei ther GH or GHRH and it is restored by substances that inhibit hypothal amic somatostatin release. Because in children the GH response to GHRH is not affected by previous neurohormone administration, it has been suggested that in childhood a GH increase is not able to trigger the s omatostatin-mediated negative GH autofeedback mechanism. To verify thi s hypothesis, in 25 children (8 girls and 17 boys; 15 prepubertal and 10 in pubertal stages II-IV) with familial short stature (normal heigh t velocity and insulin-like growth factor I levels) we studied the eff ect of acute iv administration of different recombinant human GH doses (group 1, N = 5, 0.06 U/kg; group 2, N = 6, 0.01 U/kg; group 3, N = 7 , 0.005 U/kg at - 150 min) or saline on the GH response to GHRH (1 mu g/kg iv at 0 min). In another group (N = 7), we studied the effect of 0.005 U/kg iv recombinant human GH or saline on the GH response to GHR H combined with arginine (0.5 g/kg iv over 30 min), which likely inhib its hypothalamic somatostatin release. Serum GH increases after recomb inant human GH were dose-dependent (GH peak, mean +/- SEM, 171.7 +/- 2 4.4, 33.3 +/- 3.9 and 21.8 +/- 5.1 mu g/l, respectively). The administ ration of recombinant human GH strongly inhibited the GHRH-induced GH rise in all groups (group 1, 7.1 +/- 1.7 vs 23.1 +/- 7.6 mu g/l, p < 0 .05; group 2, 9.5 +/- 2.8 vs 26.9 +/- 8.5 mu g/l, p < 0.05; group 3, 9 .1 +/- 2.7 vs 34.8 +/- 7.2 mu g/l, p < 0.02). The GH response to argin ine + GHRH (56.9 +/- 13.3 mu g/l) was higher than that to GHRH alone r ecorded in group 1 (p < 0.005), group 2 (p < 0.01) and group 3 (p < 0. 01), while exogenous recombinant human GH failed to inhibit it (45.0 /- 9.4 mu g/l). Our results demonstrate that in childhood, as well as in adulthood, recombinant human GH administration inhibits the somatot rope responsiveness to GHRH. This inhibitory effect is likely to be me diated by hypothalamic somatostatin release.