Downregulated androgen receptor expression in preputial tissues of children with hypospadias

Abstract

Purpose: To resolve conflicting evidence on androgen receptor (AR) expression in hypospadias, we compared preputial AR levels between affected children and controls. Methods: Forty patients with isolated hypospadias (age 2.9 ± 0.79 years, range 1.6–5.2 years) and 40 normal boys (age 3.2 ± 0.79 years, range 1.8–4.7 years) who underwent circumcision for phimosis were included in our study. Inner plates of preputial tissues were analyzed by immunohistochemistry for AR detection. Results: AR immunoreactivity was predominantly localized to the basal epithelial layer. Significantly reduced AR expression was observed in hypospadias patients vs. controls [average optical density (AOD), 0.38 ± 0.09 vs. 0.56 ± 0.11]. However, there was no difference in AR expression between the proximal and distal hypospadias (AOD, 0.40 ± 0.07 vs. 0.37 ± 0.10, P = 0.22). Conclusions: Preputial AR downregulation in hypospadias implicates AR deficiency in pathogenesis, providing evidence to resolve a key controversy in the field.