Testosterone regulates myosin II isoforms expression and functional activity in the rat prostate

Prostate. 2018 Dec;78(16):1283-1298. doi: 10.1002/pros.23702. Epub 2018 Aug 2.

Abstract

Background: 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.

Aims: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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).

Keywords: benign prostatic hyperplasia; myosin II; non-muscle; smooth muscle; testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Myosin Type II / metabolism*
  • Prostate / drug effects*
  • Prostate / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / pharmacology*

Substances

  • Testosterone
  • Myosin Type II