Fluorescent images were captured on a Zeiss Axiovert microscope. antibodies to CD31 and Ki-67. Results In prostates from intact mice, vascular density was highest in the proximal region and lowest in the distal region. Administration of testosterone to castrated mice increased vascular density to the greatest extent in the distal and intermediate regions. The increase in vascular density required VEGF and the angiopoietins. Endothelial cell proliferation was less sensitive to androgen in the proximal region than the remainder of the prostate. Conclusions Vascular density is usually highest in the proximal region of the prostate, but the proximal vessels are less responsive to testosterone. The SR 59230A HCl prostate is usually androgen-sensitive, but hormone sensitivity differs in the different regions of the organ. After castration of rodents, the prostate involutes to one-third to one-fifth of its normal size. Involution is usually accompanied by apoptosis of prostate epithelial cells (1). The majority of the epithelial cell loss during involution occurs in the distal region of the gland, whereas the proximal region remains largely intact (2). Upon administration of testosterone to castrated animals, SR 59230A HCl the prostate regenerates to its original size. During regeneration, epithelial proliferation is usually highest in the distal region (3). The localized response to androgens is usually consistent with what is known about the location of prostate stem cells. Cells that divide infrequently, a hallmark of stem cells, are predominantly located in the proximal region of the ducts (4). Cells isolated from the proximal region have a greater proliferative potential, a greater ability to form duct-like structures in vitro, and a greater capacity to regenerate prostatic organs in vivo than cells isolated from the remainder of the organ (4,5). In addition, cells isolated from the proximal region can survive implantation into a castrated animal and later regenerate an intact prostate upon administration of testosterone, whereas cells from the remainder of the prostate do not survive in an androgen ablated animal (5). The proximal region also expresses higher levels of TGF-, and TGF- activity appears to be important in regulating the quiescence of this region (6,7). These observations suggest that the stem cells reside in the proximal region where they are protected from the effects of androgen ablation, whereas the transit amplifying cells (proliferative cells with a limited lifespan) are predominantly located in the distal region and are sensitive to the effects of androgen. The vasculature of the prostate also responds to androgens. In castrated animals, vascular density in the prostate decreases. Indeed, apoptosis of the blood vessel endothelial cells precedes that of the epithelial cells (8). Upon restoration SR 59230A HCl of testosterone to castrated animals blood vessel endothelial cells proliferate in parallel with the epithelial cells (9,10), and vascular density increases. The vascular response to androgens is usually SR 59230A HCl mediated by angiogenic growth factors that are produced in an androgen-dependent manner by prostatic cells. Regeneration of the prostate in testosterone-treated castrated mice can be inhibited by soluble receptors for two endothelial cell-specific ligands, vascular endothelial growth factor (VEGF) and angiopoietins. The tight association between vascular and epithelial response to androgen suggests that there might also be regional differences in the vascular response similar to the regional response of the epithelial cells. We have examined if there are regional differences in vascular density in the mouse prostate and Rabbit Polyclonal to PDCD4 (phospho-Ser67) in the vascular response to androgen ablation and androgen repletion. Materials and Methods Animals Two-month-old athymic NCr male mice were purchased from the National.