Chen Ping, Xiao He, Huang Wei, Xu De-Qiang, Guo Yu-Ming, Wang Xiao, Wang Xing-Huan, DiSanto Michael E, Zhang Xin-Hua
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China.
Department of Urology, People's Hospital of Tuanfeng County, Hubei, China.
Prostate. 2018 Dec;78(16):1283-1298. doi: 10.1002/pros.23702. Epub 2018 Aug 2.
Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and prostatic volume. At the molecular level, SM myosin II (SMM II) and non-muscle myosin II (NMM II) mediate SM tone and cell proliferation while testosterone (T) plays a permissive role in the development of BPH.
The novel objective of this study was to elucidate the effects of T on the proliferation and apoptosis of rat prostatic cells and SM contractility as well as related regulatory signaling pathways.
Briefly, 36 male rats were divided into three groups (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, competitive RT-PCR, Western-blotting analysis, Masson's trichrome staining, and immunofluorescence staining were performed.
Our data showed that castration dramatically increased prostatic SM contractility and SM MHC immunostaining revealed a relatively increased SM cell numbers in the stroma. T deprivation altered prostate SMM II isoform composition with upregulation of SM-B and SM2 but downregulation of LC17a, favoring a faster more phasic-type contraction. Moreover, protein expressions of MLCK, p-MLCP, RhoB, ROCK1, and ROCK2 increased in castrated rats. Meanwhile NMM II heavy chain isoforms A, B, and C (NMMHC-A, B, and C isoforms) were altered by castration which may be linked to decreased cell proliferation and increased apoptosis.
Our novel data demonstrated T regulates SMM II and NMM II and their functional activities in rat prostate and T ablation not only decreases prostate size (static component) but also changes the prostatic SM tone (dynamic component).
良性前列腺增生（BPH）主要由前列腺平滑肌（SM）张力增加和前列腺体积增大引起。在分子水平上，SM肌球蛋白II（SMM II）和非肌肉肌球蛋白II（NMM II）介导SM张力和细胞增殖，而睾酮（T）在BPH的发生发展中起促进作用。
本研究的新目标是阐明T对大鼠前列腺细胞增殖和凋亡、SM收缩性以及相关调节信号通路的影响。
简而言之，将36只雄性大鼠分为三组（假手术组、手术去势组和去势并补充T组）。进行了体外器官浴研究、竞争性逆转录聚合酶链反应（RT-PCR）、蛋白质印迹分析、Masson三色染色和免疫荧光染色。
我们的数据表明，去势显著增加了前列腺SM收缩性，SM肌球蛋白重链（SM MHC）免疫染色显示基质中SM细胞数量相对增加。T缺乏改变了前列腺SMM II同工型组成，SM-B和SM2上调，而LC17a下调，有利于更快的更具阶段性的收缩。此外，去势大鼠中肌球蛋白轻链激酶（MLCK）、磷酸化肌球蛋白轻链磷酸酶（p-MLCP）、RhoB、Rho相关卷曲螺旋蛋白激酶1（ROCK1）和ROCK2的蛋白表达增加。同时，去势改变了NMM II重链同工型A、B和C（NMMHC-A、B和C同工型），这可能与细胞增殖减少和凋亡增加有关。
我们的新数据表明，T调节大鼠前列腺中的SMM II和NMM II及其功能活性，T切除不仅减小了前列腺大小（静态成分），还改变了前列腺SM张力（动态成分）。
