ABSTRACT
The growth of interest in clinical uses for growth hormone (GH) has largely been fueled by the unlimited supplies made available through recombinant technology since 1985. The seminal observation by Bowers et al. that met-enkephalin analogs could stimulate secretion of growth hormone from pituitary cells (1), followed by the continuing refinement of GH secretagogues (GHSs) to improve specificity of hormonal stimulation (2) has, in itself, led to a growing field of study that may improve our understanding of the control of endogenous GH secretion. Although it has been demonstrated that the GH-releasing peptides (GHRPs) elicit GH release in humans when delivered intravenously (3), intranasally (4), or orally (5), their bioavailability is limited. Consequently, much effort has been put toward the development of low molecular weight compounds that mimic the action of the GHRPs through binding at the same receptor (68). These compounds allow improved oral bioavailability compared with peptides and may expand the potential clinical usefulness of GH secretagogues. The first of these compounds L-629,429, is a nonpeptidyl benzolactam (9). In 1995, Patchett et al. described L-163,191 (MK-0677), a spiropiperidine GHRP mimetic with good oral activity (10). These two compounds, as well as GHRP6, GHRP-2, and hexarelin* have been studied in humans in several patient populations. Although the differences among these compounds will be highlighted, for the purpose of this review, GH secretagogues will refer to the GHRPs and GHRP mimetics that act through the same recently described receptor (11, 12).
