Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Apoptosis and its augmentation by androgen withdrawal is an important eventin the testis. In other tissues apoptosis is regulated by genes belongingto the bcl-2 family. However, little is known about these pathways in thehuman testes. Human testes were obtained from patients with prostatecancer, undergoing orchidectomy for permanent androgen ablative treatment.The patients were either untreated or had previously received short- orlong-term anti-androgen therapy by cyproterone acetate or GnRH agonist(goserelin). In comparison with untreated patients, testicular testosteroneconcentrations were reduced by 83% in patients treated with cyproteroneacetate and by 99% in patients treated with goserelin. Apoptotic cells wereidentified in tissue sections by in-situ end labelling of fragmented DNA.The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase(PARP) was demonstrated in tissue extracts by Western blotting. Apoptoticgerm cells were present in the spermatogenic epithelium of untreatedpatients and patients who received short-term anti-androgen treatment.There were few or no apoptotic cells in the seminiferous tubules followinglong-term anti-androgen treatment. Following short- term treatment, theconcentrations of the apoptosis-related proteins examined did not change.However, in the long-term treated testes, Bcl- xl and PARP expressiondeclined, Bax and p53 protein concentrations were unchanged, and Bcl-2 wasup-regulated. In conclusion, apoptosis occurs in spermatogenic cells of thehuman testis and may contribute to the regulation of germ cell populations.The apoptosis-related gene products which have been described in othertissues are present in the human testis and are modulated by androgenicstimuli.