Signal transduction defects in growth hormone insensitivity.
Growth hormone (GH) insensitivity is a heterogeneous condition that can result from mutations within the GH receptor (GHR) and that can be inherited as both an autosomal recessive and a dominant trait. However, evidence from a small number of growth hormone binding protein (GHBP)-positive families indicates that their GH insensitivity is independent of GHR mutations. Two of these families appear to have distinct abnormalities in GH signal transduction. Studies suggest that one family (classic Laron syndrome phenotype; designated family H) have a signalling defect close to the GHR, preventing activation of both the STAT and MAPK pathways, whereas the other family (less marked phenotype; family M) have a defect in activating MAPK but not the STAT pathway. The children studied here are specifically insensitive to GH and their defect must be exclusive to this signalling system. Thus, families with GHBP-positive GH insensitivity without GHR mutations are likely to be important models in which to study the specificity of GH signal transduction and the relationship between GH insensitive phenotype and signalling defect.
Clayton
P E
PE
Endocrine Science Research Group, University of Manchester, UK.
Freeth
J S
JS
Whatmore
A J
AJ
Ayling
R M
RM
Norman
M R
MR
Silva
C M
CM
D001827:Body Height / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics*; D013577:Syndrome
D011986:Receptors, Somatotropin