title: Is perinatal neuroendocrine programming involved in the developmental origins of metabolic disorders?
abstract: The discovery that small size at birth and during infancy are associated with a higher risk of diabetes and related metabolic disease in later life has pointed to the importance of developmental factors in these conditions. The birth size associations are thought to reflect exposure to adverse environmental factors during early development but the mechanisms involved are still not fully understood. Animal and human work has pointed to the importance of changes in the set-point of a number of key hormonal systems controlling growth and development. These include the IGF-1/GH axis, gonadal hormones and, in particular, the systems mediating the classical stress response. Several studies show that small size at birth is linked with increased activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in adult life. More recent human studies have shown associations between specific adverse experiences during pregnancy, such as famine or the consumption of adverse diets, and enhanced stress responses many decades later. The mediators of these neuroendocrine responses are biologically potent and are likely to have a direct influence on the risk of metabolic disease. These neuroendocrine changes may also have an evolutionary basis being part of broader process, termed phenotypic plasticity, by which adverse environmental cues experienced during development modify the structure and physiology of the adult towards a phenotype adapted for adversity. The changes are clearly advantageous if they lead to a phenotype which is well-adapted for the adult environment, but may lead to disease if there is subsequent overnutrition or other unexpected environmental conditions.
authors.affiliation: David IW Phillips, MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom.
authors.forename: David Iw
authors.initials: DI
authors.lastname: Phillips
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Matthews