Current Issues on Molecular Diagnosis of GH Signaling Defects.

Current Issues on Molecular Diagnosis of GH Signaling Defects. Endocr Dev. 2013;24:118-27 Authors: Feigerlova E, Hwa V, Derr MA, Rosenfeld RG 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. PMID: 23392100 [PubMed - in process]
Source: Endocrine Development - Category: Endocrinology Authors: Tags: Endocr Dev Source Type: research