title: Current issues on molecular diagnosis of GH signaling defects.
abstract: The growth-promoting effects of GH are mediated primarily by regulating the biosynthesis of insulin-like growth factor (IGF)-1. The binding of circulating GH to the cell surface GH receptor (GHR) initiates signaling cascades, of which the signal transducer and activator of transcription (STAT)-5b pathway has proven, in both rodent models and human case studies, to be the most critical in regulating IGF-1 production. The identification of rare inactivating STAT5B mutations in children, whose severe postnatal growth retardation was associated with GH insensitivity (GHI) and IGF-1 deficiency, confirmed the importance of STAT5b in regulating IGF-1 gene expression. Unlike GHI due to mutations in the GHR gene, patients carrying STAT5B mutations often present with immune dysfunction that can lead to severe, life-threatening infections and chronic pulmonary disease, consistent with the fact that STAT5b is activated by multiple cytokines involved in immunity. The possibility of a STAT5b disorder should be considered, therefore, when children present with chronic infection and/or unexplained pulmonary disease concomitant with severe postnatal growth failure.
authors: Department of Pediatrics, Oregon Health and Science University, Portland, Oreg., USA.
authors: Eva
authors: E
authors: Feigerlova
authors: Vivian
authors: V
authors: Hwa
authors: Michael A
authors: MA
authors: Derr
authors: Ron G
authors: RG
authors: Rosenfeld
mesh_terms: D000818:Animals; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics*; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism; D012377:Rodentia; D050799:STAT5 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone