Age-related variations in the growth hormone response to growth hormone secretagogues

Abstract

Growth hormone (GH) secretagogues are synthetic peptidyl and non-peptidyl molecules which possess a strong, dose-dependent and reproducible GH-releasing effect after intravenous and even oral administration in humans. This effect is probably mediated via the activation of specific receptors, mainly present at the pituitary and hypothalamic level; a human pituitary GH secretogogue receptor has already been cloned, pointing to the existence of an endogenous GH secretagogue-like ligand. The GH-releasing effect of GH secretagogues is gender-independent but undergoes marked age-related variations. In fact, the effect is low at birth, increases markedly at puberty, persists at a similar level in adulthood and decreases thereafter, being already similar in middle age to that in elderly subjects. It is likely that the reduced activity of GH secretagogues in aging reflects the age-related changes in the neural control of somatotrope function. These could include the hypothetical impairment in the activity of the putative natural GH secretagogue-like ligand. Prolonged treatment with non-peptidyl GH secretagogues has been shown to restore spontaneous GH pulsatility and insulin-like growth factor I (IGF-I) levels in aged humans as well as in animals. The possibility that chronic treatment with GH secretagogues in aging rejuvenates the activity of the GH/IGF-I axis and counteracts the age-related changes in body composition, structure functions and metabolism seems very attractive.