Figure 1. Physiology of the GH-IGF-I Axis. Release of GHRH from the hypothalamus is under the control of somatostatin (inhibitory) and Ghrelin (stimulatory). Alterations in GHRH tone led to pulsatile release of GH from the anterior pituitary. GH has widespread effects on muscle, fat and in the growth plate. IGF-I is produced in liver and in local tissues in response to GH stimulation. Red lines indicate feedback loops. Figure reproduced and adapted from Butcher I Molecular and Metabolomic Mechanisms Affecting Growth in Children Born Small for Gestational Age PhD thesis University of Manchester 2013.