Hypothalamic growth hormone-insulin-like growth factor-I axis across the human life span

The activity of the growth hormone (GH)-insulin-like growth factor-I (IGF-I ) axis undergoes marked variations across the human life span, mainly refle cting age-related changes in the neural control of somatotroph function. IG F-I secretion generally reflects GH status, except in newborns, who secrete high levels of GH but low levels of IGF-I. Changes in the gonadal steroid milieu, particularly estradiol, play a major role in the enhanced activity of the GH-IGF-I axis at puberty and probably reflect further changes in the neuroendocrine control of somatotroph secretion. The change in responsiven ess of somatotrophs to various stimuli, including GHRH, is not as marked as the spontaneous secretion of GH at puberty. However, in childhood, somatot rophs are unusually refractory to the somatostatin-mediated negative GH aut ofeedback mechanism. Normal children show normal responsiveness to the stim ulatory influence of alpha -adrenergic and cholinergic agonists, galanin an d arginine, but the activating effect of these stimuli on somatotroph secre tion is reduced in elderly individuals, with the notable exception of argin ine. Arginine potentiates both spontaneous and GHRH-induced GH secretion to the same extent in normally growing children, adults and elderly individua ls, indicating that the releasable pool of GH is generally preserved across the human life span. Thus, the reduction in spontaneous and GHRH-induced G H secretion in the elderly probably reflects age-related changes in neurotr ansmitter control, leading to GHRH hypoactivity and absolute or relative so matostatin hyperactivity in the aged hypothalamus. Cholinergic impairment i n the aging brain probably involves hypothalamic pathways and leads to decr eased activity of the GH-IGF-I axis in normal and elderly individuals, as w ell as in individuals with premature brain aging. However, there is evidenc e indicating that age-related variations in the activity of the natural GH- secretagogue ligand(s) at the hypothalamic level could also play a role in the age-dependent changes in the GH-IGF-I axis.