GH secretagogues in aging

Growth hormone (GH) secretagogues (GHS) are synthetic peptidyl and nonpepti dyl molecules which possess strong, dose-dependent and reproducible GH-rele asing activity, even after oral administration. GHS release GH via actions on specific receptors at the pituitary and, mainly, at the hypothalamic lev el. GHS likely act as functional SS antagonists and meantime enhance the ac tivity of growth hormone-releasing hormone (GHRH)-secreting neurons. In fac t, GHS need the integrity of hypothalamus-pituitary unit to fully show thei r GH-releasing effect. The GH-releasing effect of GHS is reduced in aging l ikely :reflecting concomitant GHRH hypoactivity and somatostatinergic hyper activity, though impaired activity of the putative GHS-like ligand and/or r eceptors has also to be taken into account. Orally active GHS have been pro posed as rejuvenating anabolic treatment of somatopause (age-related change s in metabolism, structure functions, and body composition partially reflec ting 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 none ndocrine 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 ac tivities including protection against cardiac ischemia and cardiomyocyte ap optosis as well as increase in cardiac contractility. These "other than GH" central and peripheral activities are now carefully under evaluation.