Lifetime Regulation of Growth Hormone (GH) Secretion

Dynamic characteristics of the growth hormone (GH) axis are determined in part by developmental age, including fetal, neonatal, childhood, pubertal, young–adult and older–adult stages of life. The growth-promoting pituitary-dependent GH axis mediates soft-tissue and skeletal growth in puberty, and maintains body composition within relatively narrow bounds in puberty and adulthood. The hypothalamo–pituitary unit comprises a unique neuroendocrine interface, in which intermittent brain signals are delivered via a finite portal microvasculature to the multicellular anterior pituitary gland. The GHRH receptor is a GTP–dependent adenylyl cyclase–activating protein, with sequence homology to secretin and vasoactive intestinal polypeptide (VIP) receptors. The prototypical endogenous GHS is ghrelin, a 28–amino acid acylated peptide, which requires an octanoyl group esterified to serine in N-terminal position 3 for maximal receptor activation. Other fatty acyl groups can also confer bioactivity. Low pulsatile GH secretion in aged individuals may be reversed acutely by simultaneous administration of GHRH, GHS and L–arginine.