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).
The Prostate. 2018 Aug 02 [Epub ahead of print]
Ping Chen, He Xiao, Wei Huang, De-Qiang Xu, Yu-Ming Guo, Xiao Wang, Xing-Huan Wang, Michael E DiSanto, Xin-Hua Zhang
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China., Department of Urology, People's Hospital of Tuanfeng County, Hubei, China., Department of Urology, People's Hospital of Wuhan University, Wuhan, China., Departments of Biomedical Sciences and Surgery, Cooper Medical School of Rowan University, Camden, New Jersey.