Do growth hormone-releasing peptides act as ghrelin secretagogues?

NN703 is an orally active and selective growth hormone secretagogue (GHS) t hat was derived from growth hormone-releasing peptide-1(GHRP-1) via ipamore lin by a peptidomimetic approach and has now entered into phase II clinical trials. When the disposition in rats of NN703 and GHRP-6 was studied using whole-body autoradiography following administration of an iv dose of radio labeled material, we found that a substantial amount of these secretagogues accumulate in the glandular part of the stomach. Because this is the site of synthesis and secretion of ghrelin, the endogenous GHS, we investigated the effect of resection of the gastrointestinal (GI) tract on growth hormon e(CH) release induced by GHRP-6. This procedure significantly attenuated th e GH secretion response by 60-70%, By contrast, the effect of CH-releasing hormone on GH release was not inhibited. The binding of GHRPs to the glandu lar part of the stomach and the blunted GH response to GHRP-6 following res ection of the G1 tract suggest a role for ghrelin as a mediator of part of the GH-releasing effect of GHRPs.