Molecular Human Reproduction, Vol 4, 701-707, Copyright © 1998 by Oxford University Press
I Woolveridge, AA Bryden, MF Taylor, NJ George, FC Wu and ID Morris
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 pathways in the
human testes. Human testes were obtained from patients with prostate
cancer, undergoing orchidectomy for permanent androgen ablative treatment.
The patients were either untreated or had previously received short- or
long-term anti-androgen therapy by cyproterone acetate or GnRH agonist
(goserelin). In comparison with untreated patients, testicular testosterone
concentrations were reduced by 83% in patients treated with cyproterone
acetate and by 99% in patients treated with goserelin. Apoptotic cells were
identified 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. Apoptotic
germ cells were present in the spermatogenic epithelium of untreated
patients and patients who received short-term anti-androgen treatment.
There were few or no apoptotic cells in the seminiferous tubules following
long-term anti-androgen treatment. Following short- term treatment, the
concentrations of the apoptosis-related proteins examined did not change.
However, in the long-term treated testes, Bcl- xl and PARP expression
declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was
up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the
human testis and may contribute to the regulation of germ cell populations.
The apoptosis-related gene products which have been described in other
tissues are present in the human testis and are modulated by androgenic
stimuli.
JOURNAL ARTICLE
Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment
Division of Physiology, Pharmacology and Toxicology, School of Biological Sciences, University of Manchester, UK.
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