Profile of cell proliferation and apoptosis activated by the intrinsic and extrinsic pathways in the prostate of aging rats

Abstract

Our findings reveal that, as the animals age, there is an increase of proliferation in restricted areas of the prostate epithelium, and a concomitant reduction of the apoptosis rate with an increase in cell survival induced by caspase-8, indicating a focused and spontaneous disruption of tissue homeostasis.

Reduced vitamin D receptor (VDR) expression and plasma vitamin D levels are associated with aging‐related prostate lesions

“…One of the main effects of the vitamin D signaling pathway on the prostate is the inhibition of cell proliferation, either by blocking the G1 to S phase cell cycle transition or by attenuating cell growth stimulating factors . Accordingly, the observed increase in VDR expression at 12 months onwards corroborates previous works from our laboratory showing that the normal prostate epithelium of older rats presents lower rates of cell proliferation than the prostate epithelium of young animals . In addition, the rat ventral prostate, which is the lobe less affected by spontaneous age‐related or androgen‐induced proliferative disorders, is also the region where we observed the highest VDR expression.…”

“…Image analysis revealed that, although the nuclear VDR intensity did not change when positive epithelial cells were considered (Figure C), a significant increase in the number of VDR‐negative cells in IP areas was observed when compared to the adjacent normal epithelium (Figure D). As higher rates of cell proliferation are found in these punctual areas of the aging rat prostates, we investigated whether the increased number of cells lacking VDR were proliferating cells. Colocalization of VDR and the proliferation marker MCM7 revealed that many of the proliferating cells found in IP areas, but not in the adjacent normal epithelium, were also negative for VDR.…”

“…The NBF-fixed prostatic complex, comprising the ventral, dorsal, lateral, and anterior prostate lobes, was dissected and embedded in paraffin for immunohistochemistry and immunofluorescence. In addition to aging, the ventral prostates of castrated and sham rats (4 months of age) were obtained as described 26 and processed for paraffin embedding.…”

“…It is well known that advancing age is the major risk factor for the development of prostate lesions that affect tissue homeostasis and may even progress to cancer . However, the occurrence of age‐dependent variation in VDR expression as well as its association with prostatic disorders is still poorly understood.…”

“…It is well known that advancing age is the major risk factor for the development of prostate lesions that affect tissue homeostasis and may even progress to cancer. [24][25][26][27] However, the occurrence of age-dependent variation in VDR expression as well as its association with prostatic disorders is still poorly understood. Therefore, in the present study, we mapped the expression pattern of VDR in the prostates of young adults to senile Wistar rats, since this animal model has the advantage of naturally developing aging-related prostate lesions that mimic most of those affecting the human prostate.…”