APOPTOSIS AND EXPRESSION OF APOPTOTIC REGULATORS IN THE HUMAN TESTIS FOLLOWING SHORT-TERM AND LONG-TERM ANTIANDROGEN TREATMENT

Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pa thways in the human testes. Human testes were obtained from patients w ith prostate cancer, undergoing orchidectomy for permanent androgen ab lative treatment. The patients were either untreated or had previously received short- or long-term anti-androgen therapy by cyproterone ace tate or GnRH agonist (goserelin). In comparison with untreated patient s, testicular testosterone concentrations were reduced by 83% in patie nts treated with cyproterone acetate and by 99% in patients treated wi th goserelin. Apoptotic cells were identified in tissue sections by in -situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl , Bar, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients wh o received short-term anti-androgen treatment. There were few or no ap optotic cells in the seminiferous tubules following longterm anti-andr ogen treatment. Following short-term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in th e long-term treated testes, Bcl-xl and PARP expression declined, Bar a nd p53 protein concentrations were unchanged, and Bcl-2 was up-regulat ed. In conclusion, apoptosis occurs in spermatogenic cells of the huma n testis and may contribute to the regulation of germ cell populations . The apoptosis-related gene products which have been described in oth er tissues are present in the human testis and are modulated by androg enic stimuli.