Effect of epidermal growth factor and testosterone on androgen receptor activation in urethral plate fibroblasts in hypospadias

Abstract

To investigate androgen receptor (AR) expression and the effect of epidermal growth factor (EGF) and testosterone on AR expression level. EGF or different concentrations of testosterone were incubated with the primary urethral plate fibroblasts from patients with hypospadias. The levels of AR expression in the fibroblasts were detected by immunocytochemical assays and graphical analysis. There was no significant difference in AR activation under physiological concentrations (3×10(-8) mol/L) of testosterone between the control and the distal hypospadias group (P>0.05). However, there was a significant decrease in AR activation in the proximal hypospadias group compared to that in the control group (P<0.001). Under the concentration of 3×10(-6) mol/L, the effects of testosterone on AR activation were dramatically different in the three groups (control group>distal hypospadias group>proximal hypospadias group, P<0.001). AR activation level in the group of proximal hypospadias was improved most obviously when EGF and physiological concentration of testosterone were employed in the urethral plate fibroblasts from hypospadias patients (P<0.001), and it was improved more in the distal hypospadias group than that in the control group (P=0.02). AR expression and activation in the urethral plate fibroblasts from hypospadias patients are abnormal. EGF can be used to improve AR activation in fibroblasts from different types of hypospadias, especially in the proximal type.