Short stature by mutant growth hormones.
Although the presence of a short stature caused by biologically inactive growth hormone (GH) has been presumed by many case reports, its molecular basis has been unclear until recently. Short stature with low concentrations of insulin-like growth factor-I (IGF-I), despite normal to high GH concentration, suggests impaired GH effect. Recently, we have reported two unique point mutations in the GH1 gene in short children whose GH was thought to be bioinactive. The mutant GH, D112G, was found to lose the capability to transduce GH-dependent signals by impaired dimerization of GH receptors. This case was the first example that proved the molecular mechanism of bioinactive GH syndrome. Another mutant GH, R77C, was so unique that it failed to stimulate GH-induced tyrosine phosphorylation in the cells by itself, but also inhibited the activity of wild-type GH, indicating an antagonistic effect of this mutant GH. The severity of short stature and the responses to exogenous GH were different in these cases. It was supposed that the molecular heterogeneity of mutant GH reflected clinical phenotypes of bioinactive GH syndrome.
Takahashi
Y
Y
Department of Medicine, Kobe University School of Medicine, Japan. takahash@med.kobe-u.ac.jp
Chihara
K
K
D001665:Binding Sites; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism; D013577:Syndrome
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I