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Vol. 71, Suppl. 2, 2009
Issue release date: April 2009
Horm Res 2009;71(suppl 2):36–40

The Growth Hormone Cascade and Its Role in Mammalian Growth

Rosenfeld R.G. · Hwa V.
aLucile Packard Foundation for Children’s Health, Stanford University, Palo Alto, Calif., and bOregon Health & Science University, Portland, Oreg., USA

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The myriad actions of growth hormone (GH) are still incompletely understood, despite decades of research. Although it is a major regulator of post-natal growth in mammals, much of its effects on skeletal growth are recognized to be mediated indirectly, through the stimulation of production of insulin-like growth factor (IGF)-I, as well as some of the major serum carrier proteins for IGF-I and -II, such as IGF-binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). The regulation of IGF-I production by GH appears to be mediated entirely by signalling through the Janus kinase (JAK) 2 pathway, via the phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT) 5b. GH also signals, however, through additional pathways that are likely to be critical to the metabolic actions of GH.

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  1. Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A: Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 2001;229:141–162.
  2. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J: Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev 1994;15:369–390.
  3. Woods KA, Camacho-Hubner C, Savage MO, Clark AJ: Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor 1 gene. N Engl J Med 1996;335:1363–1367.
  4. Walenkamp MJ, Karperien M, Pereira AM, Hilhorst-Hofstee Y, van Doorn J, Chen JW, Mohan S, Denley A, Forbes B, van Duyvenvoorde HA, van Thiel SW, Sluimers CA, Bax JJ, de Laat JA, Breuning MB, Romijn JA, Wit JM: Homozygous and heterozygous expression of a novel insulin-like growth factor-1 mutation. J Clin Endocrinol Metab 2005;90:2855–2864.
  5. Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, Kiess W, Klammt J, Kratzsch J, Osgood D, Pfaffle R, Raile K, Seidel B, Smith RJ, Chernausek SD; Intrauterine Growth Retardation (IUGR) Study Group: IGF-1 receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med 2003;349:2211–2222.
  6. Lichanska AM, Waters MJ: How growth hormone controls growth, obesity and sexual dimorphism. Trends Genet 2008;24:41–47.
  7. Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI: Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 1987;330:537–543.
  8. Godowski PJ, Leung DW, Meacham LR, Galgani JP, Hellmiss R, Keret R, Rotwein PS, Parks JS, Laron Z, Wood WI: Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci USA 1989;86:8083–8087.
  9. Lanning NJ, Carter-Su C: Recent advances in growth hormone signaling. Rev Endocr Metab Disord 2006;7:225–235.
  10. de Vos AM, Ultsch M, Kossiakoff AA: Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 1992;255:306–312.
  11. Brooks AJ, Wooh JW, Tunny KA, Waters MJ: Growth hormone receptor; mechanism of action. Intl J Biochem Cell Biol 2008;40:1984–1989.
  12. Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ: Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol 2005;12:814–821.
  13. Lichanska AM, Waters MJ: New insights into growth hormone receptor function and clinical implications. Horm Res 2008;69:138–145.
  14. Yi W, Kim SO, Jiang J, Park SH, Kraft AS, Waxman DJ, Frank SJ: Growth hormone receptor cytoplasmic domain differentially promotes tyrosine phosphorylation of signal transducers and activators of transcription 5b and 3 by activated JAK2 kinase. Mol Endocrinol 1996;10:1425–1443.
  15. Levy DE, Darnell JE Jr: Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651–662.
  16. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW: Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 1997;94:7239–7244.
  17. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN: Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 1998;93:841–850.
  18. Rowland JE, Lichanska AM, Kerr LM, White M, d’Aniello EM, Maher SL, Brown R, Teasdale RD, Noakes PG, Waters MJ: In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol 2005;25:66–77.
  19. Rosenfeld RG, Belgorosky A, Camacho-Hubner C, Savage MO, Wit JM, Hwa V: Defects in growth hormone receptor signaling. Trends Endocrinol Metab 2007;18:134–141.
  20. Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG: Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 2003;349:1139–1147.
  21. Woelfle J, Chia DJ, Rotwein P: Mechanisms of growth hormone (GH) action. Identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-1 gene activation. J Biol Chem 2003;278:51261–51266.
  22. Woelfle J, Billiard J, Rotwein P: Acute control of insulin-like growth factor-1 gene transcription by growth hormone through Stat5b. J Biol Chem 2003;278:22696–22702.

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