15. Changes in androgen receptor: immunoexpression in congenital testicular pathology

Abstract

Background Human spermatogenesis is regulated by activation of the nuclear androgen receptor (AR) of Sertoli cells. Aim AR expression has been examined in three congenital diseases with severely damaged testis and cryptorchidism (17 cases), androgen insensibility syndrome (AIS) (6 cases) and Klinefelter syndrome (9 cases). Methods Morphologic, immunohistochemical and morpho-metric evaluation, as well as PCR detection of the CAG-triplet of AR. Results In complete spermatogenesis most Sertoli cells show intense nuclear AR expression, with intensity variable from cell to cell, depending on the maturation stage of spermatogenesis, and it is completely absent in germ cells. In azoospermic human testis, AR expression in Sertoli cells is higher in number and intensity in Sertoli cell-only pattern than in those with spermatogenesis arrest, or as compared with normal testis (control group). In cryptorchidia, the tubules with disgenetic or immature Sertoli cells had no anti-AR antibody reactivity. These results suggest a direct correlation between AR expression decrease and severity of the cryptorchidic disgenetic lesions. Sertoli cells are highly disgenetic in Klinefelter syndrome and their nuclei show a variable AR-immunoexpression spectrum from moderately positive to completely negative nuclei. Conclusions AR-expression is not substantially modified in hypospermatogenic or in atrophic areas of seminiferous tubules. Testicular lesions in cryptorchidic patients, in AIS testis and in testicular biopsies of patients with Klinefelter syndrome are associated with AR immunoexpression alterations, although apparently these alterations are not due to AR important mutations, as we have not found abnormal bands of CAG-triplet of AR in cryptorchidism and AIS.