title: Histologic evaluation of human benign prostatic hyperplasia treated by dutasteride: a study by xenograft model with improved severe combined immunodeficient mice.
abstract: OBJECTIVE
  To evaluate histologic change in human prostate samples treated with dutasteride and to elucidate direct effects of dutasteride on human prostate tissue, the present study was conducted by using a xenograft model with improved severe combined immunodeficient (super-SCID) mice, although it is well known that dutasteride reduces prostate volume.
  
  
  METHODS
  After establishment of a xenograft model of human benign prostatic hyperplasia in morphology and function, samples implanted into super-SCID mice with and without dutasteride were evaluated pathohistologically at 2 and 6 months after initiation of dutasteride administration.
  
  
  RESULTS
  The proliferative index evaluated by Ki-67 staining was significantly lower in the dutasteride group than the control at 2 and 6 months after administration. Apoptotic index evaluated by the terminal transferase TdT-mediated dUTP-biotin nick end labeling staining was higher in the dutasteride group than the control at 2 and 6 months after administration. Quick scores in the dutasteride group for staining of both cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) were significantly lower than those in the control group at 2 and 6 months after administration.
  
  
  CONCLUSIONS
  Dutasteride inhibits cell proliferation and induces apoptosis of prostatic cells, causing a reduced prostate volume. Furthermore, decreased expression of Cox-2 and RhoA within benign prostatic hyperplasia tissue by dutasteride may induce an early effect on improvement of lower urinary tract symptoms, probably by attenuating inflammation reaction of the prostate and decreasing intraurethral pressure, other than the mechanism of reduced prostate volume.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: akitsuji@uro.med.osaka-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Soda
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takezawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiuchi
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takao
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: Animal Models of Human Diseases, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Animal Models of Human Diseases, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Tokita
authors.affiliation: Animal Models of Human Diseases, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Nomura
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001378:Azasteroids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000068538:Dutasteride; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D000068538:Dutasteride