Characterization of the insulin-like growth factor axis and Wilms' tumour suppressor gene in hyperparathyroidism.
BACKGROUND
Genetic mutations and upregulation of growth factors are implicated in the pathogenesis of hyperparathyroidism. The aim of this study was to evaluate the role of Wilms' tumour suppressor gene (WT-1) and the insulin-like growth factor (IGF) axis in hyperparathyroidism.


METHODS
The expression of WT-1 and IGF components was examined by immunohistochemistry, reverse transcriptase-polymerase chain reaction and western immunoblotting in a panel of parathyroid specimens from both primary and secondary hyperparathyroidism. A human parathyroid cell culture model was established to examine the parathyroid response to IGF stimulation.


RESULTS
There was a significantly lower level of WT-1 expression in parathyroid tumours than in normal parathyroid glands. Most tumours expressed IGF-I and IGF-II receptors and responded to IGF stimulation. Only IGF-I was present in normal parathyroid glands, whereas IGF-II was expressed exclusively in parathyroid tumours.


CONCLUSIONS
Abnormal expression of WT-1 and the IGF axis may play a role in the pathogenesis of hyperparathyroidism.
Department of Endocrine Surgery, Frenchay Hospital, Bristol, UK. chriswong@tiscali.co.uk
C K M
CK
Wong
T
T
Lai
S
S
White
E
E
Sheffield
M H
MH
Wheeler
C E H
CE
Stewart
J R
JR
Farndon
D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation / Q000235:genetics; D017451:Receptors, Somatomedin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013002:Somatomedins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
D017451:Receptors, Somatomedin; D013002:Somatomedins; D025721:WT1 Proteins