GROWTH-HORMONE (GH) RESPONSES TO GH-RELEASING PEPTIDE AND TO GH-RELEASING HORMONE IN GH-DEFICIENT CHILDREN

The GH-releasing peptides (GHRPs) are a family of hexa- and heptapepti des that specifically stimulate GH secretion in normal adults and chil dren. They would be an attractive potential form of therapy for GH def iciency (GHD) if they are also active in these patients. Their action, however, appears to result at least in part through hypothalamic resp onses, which may be impaired in GHD, and their ability to evoke a GH r esponse in these patients must therefore be directly examined. We stud ied GH responses to the heptapeptide GHRP-1 in 22 prepubertal children with previously documented GHD and growth failure and compared them t o responses to GHRH and the two peptides administered together. Patien ts received 1 mu g/kg GHRH-(1-44)NH2, 1 mu g/kg GHRP-1, or both, in ra ndom order. Tests were separated by at least 1 week. GHRP-1 evoked a s ignificant GH response in 60% of the patients, comparable to the 68% w ho responded to GHRH. The magnitudes of the peak responses were simila r (7.5 +/- 8.0 mu g/L to GHRP-1 and 11.2 +/- 12.1 to GHRH), although t he duration of the GH rise was briefer after GHRP-1. Both responses we re lower than those previously observed in normal subjects. There was a marked synergy in responses when the two were given together; the GH peak (34.2 +/- 44.8 mu g/L) significantly exceeded the sum of the ind ividual responses, and the proportion of patients who responded (86%) was also higher. Thus, despite the absence of endogenous GHRH reflexes in most patients with GHD, these children can respond to GHRP-1 simil arly to GHRH, and GHRP-1 can markedly enhance the response to GHRH. Th ese results suggest that GHRPs or their analogs could form the basis f or therapy of GHD.