Human GH pulsatility: an ensemble property regulated by age and gender

Age and gender impact the full repertoire of neurohormone systems, including most prominently the somatotropic, gonadotropic and lactotropic axes. For example, daily GH production is approximately 2-fold higher in young women than men and varies by 20-fold by sexual developmental status and age. Deconvolution estimates of 24-h GH secretion rates exceed 1200 microg/m2 in adolescents and fall below 60 microg/m2 in aged individuals. The present overview highlights plausible factors driving such lifetime variations in GH availability, i.e., estrogen, aromatizable androgen, hypothalamic peptides and negative feedback by GH and IGF-I. In view of the daunting complexity of potential neuromodulatory signals, we underline the utility of conceptualizing a simplified three-peptide regulatory ensemble of GHRH, GHRP (ghrelin) and somatostatin. The foregoing signals act as individual and conjoint mediators of adaptive GH control. Regulation is enforced at 3-fold complementary time scales, which embrace pulsatile (burst-like), entropic (orderly) and 24-h rhythmic (nycthemeral) modes of GH release. This unifying platform offers a convergent perspective of multivalent control of GH outflow.