Transient ischemia induces apoptosis in the ventral prostate of the rat

Abstract

The mechanisms involved in the castration-induced involution of the ventral prostate (VP) are not fully understood. It was recently reported that castration decreases blood flow in the VP in rats and that this occurs before the apoptotic involution of the organ. However, it is unknown whether a decrease in blood flow may trigger apoptosis in the VP, and this was therefore examined in this study. The right iliac artery was clamped for 1 h in adult male rats. After 24 h of reperfusion, the VPs were frozen or fixed. In situ end-labeling (ISEL) was used to identify apoptotic cells, and testosterone repressed prostatic message-2 (TRPM-2) was measured. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was used to identify proliferating cells. Clamping the right iliac artery reduced blood flow in the right VP to 0.17 of that in the contralateral lobe. This relative ischemia resulted in a threefold increase in the volume density of apoptotic epithelial cells on the treated side, but left cell proliferation unaffected. Testosterone substitution did not change this pattern. This study suggests that a transient period of relative ischemia may induce apoptosis in the rat ventral prostate. This may be of importance for the understanding of castration-induced prostatic involution.

Evidence of pluripotent human prostate stem cells in a human prostate primary xenograft model

“…The basal localization of proliferating cells, and the presence of epithelial commitment to multiple lineages, indicates repopulation of the epithelial compartment did not occur by compensatory proliferation of mature basal or secretory epithelial cells. The response of the prostate to the hypoxia induced by vascular involution secondary to androgen withdrawal [23,24] may be different then the hypoxic response caused by transplantation in an androgenic environment. The proliferation index induced by a 2 day androgen stimulation of the 2-month xenografts that had undergone epithelial involution in response to 1 month of androgen deprivation, was twofold higher then in the initial benign prostatic tissue, indicating that the prostate progenitor cells are proliferating specifically in response to the short interval of androgen stimulation, however, the increase relative to the presumably suppressed proliferation index after 1 month of androgen withdrawal was not determined in this study.…”

Inhibitory Effects of Castration in an Orthotopic Model of Androgen-Independent Prostate Cancer Can Be Mimicked and Enhanced by Angiogenesis Inhibition

“…Previous studies have shown that the magnitude of the decrease in blood flow in the ventral prostate is sufficient to cause tissue hypoxia (14) and cell death (9,10). Decreased blood supply may therefore induce apoptosis in the normal surrounding tissue (9) and in the tumor. In line with this, staining with hypoxyprobe showed increased tumor hypoxia 3 days after castration (P = 0.001; Fig.…”

Apoptotic and Proliferative Index after Alpha-1-Adrenoceptor Antagonist and/or Finasteride Treatment in Benign Prostatic Hyperplasia

“…Thus, bcl-2 upregulation may reflect the normal response of these epithelial cells after androgen ablation. Some recent studies [13][14][15] endorse that prostatic involution due to castration might be the result of a chronic and severe diminishment in blood supply to prostate. Thus, prostate epithelial cell apoptosis after castration may be more a factor of an ischemic/hypoxic condition due to reduced blood flow to the gland rather than any direct effect of androgen withdrawal on the prostate cells.…”