Current issues on molecular diagnosis of GH signaling defects

Eva Feigerlova, Vivian Hwa, Michael A. Derr, Ron G. Rosenfeld

Research output: Chapter in Book/Report/Conference proceedingChapter

18 Scopus citations


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.

Original languageEnglish (US)
Title of host publicationHormone Resistance and Hypersensitivity
Subtitle of host publicationFrom Genetics to Clinical Management
PublisherS. Karger AG
Number of pages10
ISBN (Print)9783318022674
StatePublished - 2013

Publication series

NameEndocrine Development
ISSN (Print)1421-7082
ISSN (Electronic)1662-2979

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems


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