Effects of Eight Months Treatment with Graded Doses of a Growth Hormone (GH)-Releasing Peptide in GH-Deficient Children1

Abstract

Stimulation of pituitary GH secretion with administered GHRH can be effective therapy for those GH deficient (GHD) patients whose disorder results from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasing peptides (GHRP's), which have a different mechanism of action from GHRH, with release of GH. In this study we tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over time. Six prepubertal children with GHD and growth failure received stepwise increasing s.c. doses of GHRP-2, at 0.3, 1.0, and 3.0 micrograms/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a fourth 2-month period, they received 3 micrograms/kg GHRP-2 together with 3 micrograms/kg s.c. GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, with 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 during GHRP-2 treatment than during pretreatment and post-treatment evaluations. 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.

Growth Hormone Secretagogues

“…It was well tolerated, able to stimulate GH secretion and enhanced growth velocity without side effects or toxicities in an eight months trial of prepubertal children with growth failure [14]. It has recently been shown that subcutaneous administration of GHRP-2 to lean, healthy males, like ghrelin, increases food intake [15].…”

Clinical Pharmacology of Human Growth Hormone and its Secretagogues

“…Co-administration of GHRH and atenolol, a β 1 -adrenergic antagonist that inhibits SRIH release, enhances the linear growth response to GHRH [83]. In short-term studies, administration of the GHS -GHRP-2 -with GHRH increased growth rates in short children to values above those recorded with either agent alone [100]. Although no major complications of GHRH therapy have been reported, there does not appear to be a substantial advantage to the administration of GHRH rather than hGH in most patients.…”