Growth Hormone Secretagogues: A New Era for Anabolic and Metabolic Therapies

Growth hormone (GH) plays a crucial role in growth, metabolism, and body composition. Traditional GH replacement therapy, while effective for GH deficiency, often requires daily injections and can be costly. There was a significant need for orally active compounds that could stimulate the body's own GH production, offering a more convenient and potentially safer therapeutic approach. This review synthesized the understanding of growth hormone secretagogues (GHSs) and their therapeutic potential up to 2005.

The review highlighted the discovery of ghrelin as the endogenous ligand for the GHS-R1a receptor, revolutionizing the understanding of GH regulation. Synthetic GHSs, both peptidyl (e.g., GHRP-2) and non-peptidyl (e.g., MK-677), were shown to potently stimulate GH release. For instance, MK-677 administered orally at 25 mg/day in healthy adults consistently increased mean 24-hour GH secretion by up to 60% and IGF-1 levels by 20-30% over 8 weeks. Peptidyl GHSs like GHRP-6 demonstrated a 2-3 fold increase in pulsatile GH release compared to placebo, albeit with shorter half-lives. Beyond GH, GHSs were found to have direct effects on appetite, body composition, and bone metabolism, often independent of GH. The review underscored that non-peptidyl GHSs, particularly MK-677, offered the significant advantage of oral bioavailability and sustained GH elevation, making them highly promising candidates for chronic therapeutic use.