EFFECTS OF 8 MONTHS TREATMENT WITH GRADED DOSES OF A GROWTH-HORMONE (GH)-RELEASING PEPTIDE IN GH-DEFICIENT CHILDREN

Stimulation of pituitary GH secretion with administered GHRH can he ef fective therapy for those GH deficient (GHD) patients whose disorder r esults from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasin g peptides (GHRP's), which have a different mechanism of action from G HRH, with release of GH. In this study we tested whether the GH respon se to a newer GHRP, GHRP-2, would be sustained over time. Six prepuber tal children with GHD and growth failure received stepwise increasing sc doses of GHRP-2, at 0.3, 1.0, and 3.0 mu g/kg/day, in successive a- month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a f ourth 2-month period, they received 3 mu g/kg GHRP-2 together with 3 m u g/kg sc GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administrati on produced a dosewise increase in overnight GK secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, wit h little effect upon GH secretion later in the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity was higher duri ng GHRP-2 treatment than during pretreatment and post-treatment evalua tions. There were no side effects or toxicities observed. Thus GHRP-2 is well tolerated and is able to stimulate GH secretion. Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.