Growth Hormone-Releasing Peptides May Act Through Ghrelin in the Stomach

Growth hormone-releasing peptides (GHRPs) are synthetic compounds known to stimulate the release of growth hormone (GH). Ghrelin is the body's endogenous (naturally produced) GH secretagogue, primarily synthesized and secreted from the stomach. While GHRPs are effective at stimulating GH, the precise mechanisms by which they achieve this, particularly their interaction with endogenous ghrelin pathways, have not been fully understood. This study investigated whether GHRPs exert their GH-releasing effects by acting as ghrelin secretagogues, especially given their observed accumulation in the stomach.

Whole-body autoradiography revealed that a substantial amount of both NN703 and GHRP-6 accumulated specifically in the glandular part of the stomach. This region is notably the primary site of synthesis and secretion for ghrelin, the body's natural GH secretagogue. Resection of the gastrointestinal tract significantly attenuated the GH secretion response induced by GHRP-6 by a substantial 60-70%. This quantitative reduction strongly suggests a critical role for the GI tract in mediating GHRP-6's effects. In contrast, the GH-releasing effect of GH-releasing hormone (GHRH) was not inhibited by GI tract resection, indicating a specific interaction with GHRPs rather than a general impairment of GH release. The binding of GHRPs to the stomach and the blunted GH response after GI tract resection strongly suggest that ghrelin acts as a mediator for a significant portion of the GH-releasing effect of GHRPs.