title: Androgen and prostatic stroma.
abstract: OBJECTIVE
  To investigate the effect of androgen on the proliferation, differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro.
  
  
  METHODS
  Twenty-two dogs, including 15 normal prostate dogs and 7 prostatic hyperplasia dogs, had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration. The expression of androgen receptor (AR) and estrogen receptor (ER) in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration. Light microscopy, transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT). The proliferation of the cell culture was detected by MTT assay. The expression of TGFbgr, bFGF, AR, and smooth muscle cell (SMC) specific proteins (myosin and/or smoothelin) were detected using immunohistochemistry and RT-PCR. The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins.
  
  
  RESULTS
  Before castration, the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups. Following castration, the serum concentration of testosterone decreased rapidly in 2 days, and the concentration of estrodiol had no significant change compared with the pre-castration data. In the prostate, AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues (P<0.05). While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group. Within the early phase of castration (<d7), the expression of AR was increased rapidly. Then it gradually dropped to a lower level than that of the pre-castration by the end of d90. The expression of ER remained unchanged in the whole course. The prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent serial pathological changes of atrophy and apoptosis after castration. The atrophic cells were filled with huge intracellular lipofuscin. The expression of SMC myosin declined after castration, coincident with the increase in TGFbgr mRNA level and decline in bFGF mRNA level. In vitro, DHT caused a weak increase in the proliferation and expression of SMC-specific proteins (P<0.05). However, DHT and bFGF together stimulated the proliferation of stromal cells significantly more than either agent alone (P<0.01). The combination of DHT and TGFbgr greatly enhanced the expression of SMC-specific proteins (P<0.01) more strongly than either alone (P<0.01).
  
  
  CONCLUSIONS
  The whole prostate gland is an androgen-sensitive organ with both the epithelium and stroma under the control of androgen. Androgen may direct the proliferation, differentiation and regression of stromal cells by regulating the expression of TGFbgr, bFGF, AR and smooth muscle cell specific proteins.
authors.affiliation: Department of Prostatic Disease, Tianjin Institute of Urologial Surgery, 23 Pingjiang Road, Hexi District, Tianjin 300211, China. niuyj@public.tpt.tj.cn
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Niu
authors.forename: Teng-Xiang
authors.initials: TX
authors.lastname: Ma
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Rui-Fa
authors.initials: RF
authors.lastname: Han
authors.forename: Guang
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004285:Dogs; D004958:Estradiol / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology / Q000502:physiology*; D011470:Prostatic Hyperplasia / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D013739:Testosterone / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; D013739:Testosterone; D004958:Estradiol