Login to Access Video or Poster Abstract: MP17-13
Sources of Funding: EMM is supported by an F31 (F31DK111131). DVG is supported by an R01 (CA178431).

Introduction

Benign prostatic hyperplasia (BPH) is one of the most common prostatic disorders affecting aging men, causing progressive lower urinary tract symptoms (LUTS) such as bladder outlet obstruction (BOO). While ultrasound imaging is the current standard of care in monitoring human BPH, magnetic resonance imaging (MRI) offers enhanced image resolution. BPH may result from hormone-mediated aberrant proliferation of prostate progenitor cells. Lack of sufficient in vivo models has made this hypothesis difficult to test directly. The objective of this study was to evaluate a recently published murine model of BOO/BPH via longitudinal MR imaging and immunohistochemistry to further understand the underpinning mechanisms of BPH/BOO pathophysiology.

Methods

We adapted a recently published model of prostatic enlargement in order to investigate proliferating cell populations. Briefly, post-pubescent male mice were castrated and surgically implanted with subcutaneous implants to slowly release either testosterone (T) only or testosterone and estradiol (E). Mice were evaluated using MRI at 2-4 week intervals post-castration and then sacrificed accordingly. MR imaging was used to determine prostatic, urethral, and genitourinary blood volumes. Immunohistochemistry (IHC) was used to determine proliferating cell populations and prostate lineage changes.

Results

We observed a significant increase, approximately 2-fold, in the prostatic volume of mice treated with T+E as compared to T controls (p = 0.01) with a concomitant decrease in urethral volume (p = 0.01). T+E mice also had significantly higher genitourinary blood volumes (p = 0.01), indicating more genitourinary vascularization. We found no significant difference in number of CK8+ luminal cells, CK5+ basal cells, or Ki67+ epithelial cells.

Conclusions

Using MRI and IHC, we demonstrate that long-term treatment of mice with testosterone and estradiol induces an increase in prostatic volume with a concomitant decrease in urethral volume. Despite prostatic enlargement, we did not document an increase in proliferating prostatic epithelial cells or inflammatory infiltrate. Refining murine models is essential to understanding human BPH etiology and pathology. These data are critical to development of novel strategies that target progenitor cell populations in BPH, an unmet therapeutic need.

Funding

EMM is supported by an F31 (F31DK111131). DVG is supported by an R01 (CA178431).