Growth hormone secretagogues: history, mechanism of action, and clinical development

Growth hormone secretagogues (GHSs) are a generic term to describe compounds that increase growth hormone (GH) release. GHSs include agonists of the growth hormone secretagogue receptor (GHS-R), whose natural ligand is ghrelin, and agonists of the growth hormone-releasing hormone (GHRH) receptor, to which the GHRH binds as a native ligand. Several GHSs have been developed with a view to treating or diagnosing of GH deficiency, which causes growth retardation, gastrointestinal dysfunction, and altered body composition, in parallel with extensive research to identify GHRH, GHS-R, and ghrelin. This review will focus on the research history and the pharmacology of each GHS, which reached randomized clinical trials. Furthermore, we will highlight the publicly disclosed clinical trials regarding GHSs.