title: Short and tall stature: a new paradigm emerges.
abstract: In the past, the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis was often considered to be the main system that regulated childhood growth and, therefore, determined short stature and tall stature. However, findings have now revealed that the GH-IGF-1 axis is just one of many regulatory systems that control chondrogenesis in the growth plate, which is the biological process that drives height gain. Consequently, normal growth in children depends not only on GH and IGF-1 but also on multiple hormones, paracrine factors, extracellular matrix molecules and intracellular proteins that regulate the activity of growth plate chondrocytes. Mutations in the genes that encode many of these local proteins cause short stature or tall stature. Similarly, genome-wide association studies have revealed that the normal variation in height seems to be largely due to genes outside the GH-IGF-1 axis that affect growth at the growth plate through a wide variety of mechanisms. These findings point to a new conceptual framework for understanding short and tall stature that is centred not on two particular hormones but rather on the growth plate, which is the structure responsible for height gain.
authors.affiliation: Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, MSC-1103, Bethesda, MD 20892, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
authors.affiliation: Division of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
authors.affiliation: Saint Christopher's Hospital for Children, Section of Endocrinology and Diabetes, 160 East Erie Avenue, Philadelphia, PA 19134, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Luca
authors.affiliation: Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, Division of Endocrinology, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dauber
authors.affiliation: The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Children's Diabetes, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tikva 49202, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Phillip
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, PO Box 9600, Leiden, 2300 RC, Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.affiliation: Division of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D001827:Body Height / Q000235:genetics / Q000502:physiology*; D018628:Gene Dosage; D006130:Growth Disorders / Q000235:genetics; D006132:Growth Plate; D019382:Human Growth Hormone / Q000235:genetics / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I