Current issues on molecular diagnosis of GH signaling defects

Eva Feigerlova, Vivian Hwa, Michael A. Derr, Ronald (Ron) Rosenfeld

Research output: Chapter in Book/Report/Conference proceedingChapter

13 Citations (Scopus)

Abstract

The growth-promoting effects of GH are mediated primarily by regulating the biosynthesis of insulinlike 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: From Genetics to Clinical Management
PublisherS. Karger AG
Pages118-127
Number of pages10
Volume24
ISBN (Print)9783318022681, 9783318022674
DOIs
StatePublished - Feb 4 2013

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Intercellular Signaling Peptides and Proteins
Pulmonary diseases
Defects
Mutation
Lung Diseases
Growth
STAT5 Transcription Factor
Biosynthesis
Cell Surface Receptors
Infection
Gene expression
Immunity
Rodentia
Chronic Disease
Genes
Cytokines
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Feigerlova, E., Hwa, V., Derr, M. A., & Rosenfeld, R. R. (2013). Current issues on molecular diagnosis of GH signaling defects. In Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management (Vol. 24, pp. 118-127). S. Karger AG. https://doi.org/10.1159/000342586

Current issues on molecular diagnosis of GH signaling defects. / Feigerlova, Eva; Hwa, Vivian; Derr, Michael A.; Rosenfeld, Ronald (Ron).

Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management. Vol. 24 S. Karger AG, 2013. p. 118-127.

Research output: Chapter in Book/Report/Conference proceedingChapter

Feigerlova, E, Hwa, V, Derr, MA & Rosenfeld, RR 2013, Current issues on molecular diagnosis of GH signaling defects. in Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management. vol. 24, S. Karger AG, pp. 118-127. https://doi.org/10.1159/000342586
Feigerlova E, Hwa V, Derr MA, Rosenfeld RR. Current issues on molecular diagnosis of GH signaling defects. In Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management. Vol. 24. S. Karger AG. 2013. p. 118-127 https://doi.org/10.1159/000342586
Feigerlova, Eva ; Hwa, Vivian ; Derr, Michael A. ; Rosenfeld, Ronald (Ron). / Current issues on molecular diagnosis of GH signaling defects. Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management. Vol. 24 S. Karger AG, 2013. pp. 118-127
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