Growth hormone secretagogues.
Growth hormone secretagogues (GHSs) are a class of synthetic compounds that increase growth hormone secretion and serum IGF-1 concentrations. The short-acting GHSs produce transient elevations in GH which lead to little or no changes in IGF-1; the long-acting GHSs stimulate pulsatile GH release due to sustained elevations of IGF-1. GHSs are currently undergoing evaluation as orally active alternatives to the recombinant human proteins, rhGHRH and rhGH. The clinical development of these compounds has been complicated, not by a failure to enhance GH secretion or raise IGF-1 in humans, but by the difficulty of establishing the therapeutic utility of increasing endogenous levels of GH/IGF-1 (as opposed to replacement with exogenous hormone). The phase II/III clinical trials of one GHS, MK0677 (Merck & Co Inc), for the treatment of short-stature in growth hormone-deficient children and frailty in the elderly have been discontinued for lack of sufficient efficacy. This review summarizes recent advances in this new therapeutic area and describes possible future directions.
Carpino
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Department of Cardiovascular & Metabolic Diseases, MS 8220-3004, Pfizer Central Research, Groton, CT 06340, USA. philip_a_carpino@groton.pfizer.com