良性前列腺增生症（BPH）是一种非肿瘤增生性疾病，会产生与增大的前列腺相关的下尿路症状。BPH在病理上以上皮和基质组织的过度增生为特征。雄激素信号对前列腺功能至关重要，雄激素阻断是缓解BPH症状的第二线药物治疗。本研究检测了使用前列腺素基因启动子驱动泌乳素（Pb-PRL）转基因小鼠获得的前列腺，这是一种强大的BPH模型，能自发地发展为前列腺肿大，以研究手术阉割后前列腺的消退反应。连续超声成像显示出Pb-PRL前列腺体积的非常均匀、自限制性增长，这与BPH的温和、有限细胞增殖特征一致，并与小鼠前列腺癌模型高度可变的指数增长形成了对比。与正常前列腺腺体经手术阉割引起的消退相比，阉割只引起了部分前列腺体积的减小。与阉割引起的消退相比，抗雄激素finasteride引起的Pb-PRL前列腺体积减少要少一些。Pb-PRL老鼠前列腺体积退化的程度与基质组织的初始体积相关，表明上皮和基质组织对雄激素撤退的敏感度不同。事实上，二维形态学分析揭示出Pb-PRL老鼠基质组织的消退速度明显降低。Pb-PRL前列腺基质组织中的肌成纤维细胞成分看起来是正常的，但基质组织含有更多的成纤维细胞和胶原外基质沉积。与正常前列腺一样，Pb-PRL前列腺的退化速度部分依赖于TGFß和TNF信号，但与正常前列腺不同的是，阉割引起的消退程度不受TGFß或TNF阻断的影响。我们的研究表明，雄激素剥夺可以有效地减少过度增生的前列腺的总体积，但基质组织相对耐受，这表明可能需要采取额外措施以提供有效的治疗BPH临床表现的方法。AJCEU 版权所有 © 2023。

Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.AJCEU Copyright © 2023.