[New molecular mechanisms of growth hormone insensitivity].
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.
Edouard
T
T
Service d'endocrinologie pédiatrique, hôpital des enfants, place du Docteur-Baylac, 330 avenue de Grande-Bretagne, 31059 Toulouse cedex, France. edouard.t@chu-toulouse.fr
Raynal
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P
Yart
A
A
Conte-Auriol
F
F
Salles
J-P
JP
Tauber
M
M
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005544:Forecasting; D006720:Homozygote; D019382:Human Growth Hormone / Q000097:blood / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D046150:Laron Syndrome / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics; D010641:Phenotype; D011986:Receptors, Somatotropin / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019382:Human Growth Hormone