GH Secretagogues in Aging

Abstract

Growth hormone (GH) secretagogues (GHS) are synthetic peptidyl and nonpeptidyl molecules which possess strong, dose-dependent and reproducible GH-releasing activity, even after oral administration. GHS release GH via actions on specific receptors at the pituitary and, mainly, at the hypothalamic level. GHS likely act as functional SS antagonists and meantime enhance the activity of growth hormone-releasing hormone (GHRH)-secreting neurons. In fact, GHS need the integrity of hypothalamus-pituitary unit to fully show their GH-releasing effect. The GH-releasing effect of GHS is reduced in aging likely reflecting concomitant GHRH hypoactivity and somatostatinergic hyperactivity, though impaired activity of the putative GHS-like ligand and/or receptors has also to be taken into account. Orally active GHS have been proposed as rejuvenating anabolic treatment of somatopause (age-related changes in metabolism, structure functions, and body composition partially reflecting the aging of GH/IGF-I axis). No definitive evidence of their clinical usefulness as anabolic agents has been provided yet. On the other hand, GHS have specific receptors in other central and peripheral endocrine and nonendocrine tissues. These receptor subtypes mediate GH-independent biological activities linked to the neuro-endocrinology of aging. For instance, GHS: (a) possess adrenocorticotropic hormone (ACTH)-releasing activity, which is increased in elderly subjects; (b) influence sleep pattern rejuvenating it in elderly subjects; (c) stimulate food intake; (d) have cardiovascular activities including protection against cardiac ischemia and cardiomyocyte apoptosis as well as increase in cardiac contractility. These "other than GH" central and peripheral activities are now carefully under evaluation.