Translational Neuroendocrinology: Control of Human Growth

Human growth is driven by both basic cell processes as well as hormones, in particular the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis. Understanding how these mechanisms are coordinated is not only critical to achieving a normal growth rate, but also to recognising potential new causes of disordered growth and how they might be treated. We have demonstrated in healthy children that height is gained by periods of rapid growth interspersed by periods of very slow growth or even stasis. We have also shown that a lower order organism, Caenorhabditis elegans, grows in a similar manner. By contrast, secretion of GH from somatotrophs occurs on a daily basis in discrete pulses over a 24-h period. We have used the measurement of GH in urine as a surrogate marker of GH secretion to show that there are rhythms of GH output with frequencies of several days. We then assessed which attributes of these GH profiles were related to growth and found that disorderliness in the GH profile (as measured by approximate entropy) was related to better growth rate. This feature was then tested in the dwarf rat using different GH regimens to introduce variation into the administration of daily GH injections. Better long bone growth was associated with week-to-week or even random dose variation compared to the same amount of GH delivered as a standard daily dose. Understanding the control of growth has implications in clinical practice for modelling GH treatment regimens based on physiological principles.