[New molecular mechanisms of growth hormone insensitivity].

Abstract

Growth hormone (GH), secreted by the anterior pituitary into the circulation, binds to membrane receptors in target tissues to stimulate body growth; most of its effects is mediated by the insulin-like growth factor 1 (IGF-1). In addition to promoting growth, GH has important metabolic actions. The syndrome of GH insensitivity (GHI) was first identified in 1966 by Laron et al. in three children with clinical phenotype characteristic of growth hormone deficiency but associated with elevated serum concentration of GH. Direct evidence of a GH receptor (GHR) abnormality was provided in 1989. More recently, molecular abnormalities in the postreceptor signalling mechanism were found. Mutations of signal transducer and activator of transcription 5b (Stat5b) were reported in patients with growth retardation and primary immunodeficiency. Mutations of the tyrosin phosphatase Shp2 were identified in patients affected by Noonan syndrome characterized by short stature, cardiopathy and increased risk of leukaemia. The unmasking of the molecular bases for these defects will contribute greatly to our future understanding of both normal and aberrant growth. Moreover, this knowledge should bring insight on cancerogenesis or immunodeficiency caused by cytokines resistance.

• Authors: T Edouard, P Raynal, A Yart, F Conte-Auriol, J-P Salles, M Tauber
• Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie (Arch Pediatr) Vol. 15 Issue 2 Pg. 179-88 (Feb 2008) ISSN: 0929-693X [Print] France
• Vernacular Title: Nouveaux mécanismes moléculaires impliqués dans l'insensibilité à l'hormone de croissance.
• PMID: 18207712 (Publication Type: Comparative Study, English Abstract, Journal Article, Review)

Chemical References

• Receptors, Somatotropin
• STAT5 Transcription Factor
• STAT5A protein, human
• STAT5B protein, human
• Transcription Factors
• Tumor Suppressor Proteins
• Human Growth Hormone

Topics

• Adolescent
• Adult
• Child
• Female
• Forecasting
• Homozygote
• Human Growth Hormone (blood, genetics)
• Humans
• Infant, Newborn
• Laron Syndrome (blood, genetics)
• Male
• Mutation
• Noonan Syndrome (genetics)
• Phenotype
• Receptors, Somatotropin (genetics)
• STAT5 Transcription Factor (genetics)
• Signal Transduction (genetics)
• Transcription Factors (genetics)
• Tumor Suppressor Proteins (genetics)