title: Catch-Up Growth: Basic Mechanisms.
abstract: The neuroendocrine model of catch-up growth has been well studied in a number of animal models. During nutritional inadequacy, which invariably precedes catch-up growth, growth hormone (GH) levels increase under the influence of the oxygenic 'hunger signal' ghrelin. This increase in GH would usually be accompanied by an increase in IGF-1. However, malnutrition also induces the nutritionally responsive proteins sirtuin 1 (SIRT1) and fibroblast growth factor 21 (FGF21) that block GH signal transduction in the liver by blocking the JAK/STAT pathway, limiting IGF-1 production. The result is that GH's action is shifted from hepatic effects to effects in other tissues (for example muscle and adipose) and shifted away from IGF-1-mediated effects and towards GH-mediated effects. Once nutrients become more available, SIRT1 and FGF21 levels, and hepatic GH sensitivity return to normal, and production of IGF-1 resumes. This shifts GH signaling away from GH-mediated effects, and towards IGF-1-mediated effects both in the liver and in other tissues. It presumably leads to greatly increased IGF-1 signaling that would have been expected without the prior episode of nutritional inadequacy. Although much work remains to be done, it does appear that ghrelin is increased in in utero and postnatal malnutrition, that elevations in ghrelin may be prolonged after malnutrition resolves, and that higher ghrelin levels are associated with increased rates of catch-up growth. Prolonged increases in circulating ghrelin and GH, combined with a rapid return in hepatic GH sensitivity would provide an elegant mechanism to drive catch-up growth after periods of nutritional insufficiency.
authors.affiliation: UC Davis Children's Hospital, Sacramento, CA, USA.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Griffin
mesh_terms: D000818:Animals; D004838:Epiphyses; D005346:Fibroblast Growth Factors / Q000502:physiology; D054439:Ghrelin / Q000502:physiology; D006128:Growth / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D007234:Infant, Premature; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008099:Liver / Q000503:physiopathology; D044342:Malnutrition / Q000503:physiopathology*; D023421:Models, Animal; D009490:Neurosecretory Systems; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000502:physiology; D015430:Weight Gain / Q000502:physiology*
chemical_list: D054439:Ghrelin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D056564:Sirtuin 1