Proliferation and differentiation of prostatic stromal cells

Y. Niu et al., Proliferation and differentiation of prostatic stromal cells, BJU INT, 87(4), 2001, pp. 386-393
Citations number
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
1464-4096 → ACNP
Year of publication
386 - 393
SICI code
Objectives To investigate the effects of androgen, transforming growth fact or beta1 (TGF-beta) and basic fibroblast growth factor (bFGF) on the prolif eration and differentiation of prostatic stromal cells of the dog in vivo a nd human stromal cells in vitro. Materials and methods Twenty-two dogs had their serum concentration of test osterone and oestradiol determined by radioimmunoassay before and after cas tration. Light microscopy, transmission electron microscopy and an in situ cell-death assay were carried out successively before and after castration to evaluate prostatic histomorphology. A semi-quantitative reverse transcri ptase-polymerase chain reaction (RT-PCR) was used to evaluate the expressio n of TGF-beta, bFGF and myosin in the canine prostate tissue after castrati on. In vitro serum-free cell cultures from human prostatic stroma were esta blished and exposed to dihydrotestosterone (DHT), TGF-beta and bFGF in vari ous concentrations. The proliferation of the cell cultures was detected by the tetrazolium assay. The differentiation from fibroblasts to smooth muscl e cells (SMCs) was deduced by measuring the expression of SMC-specific prot eins (myosin and smoothelin) using immunohistochemistry and RT-PCR. Results Castration resulted in a significant decrease in circulating testos terone levels (P<0.01), but did not affect the circulating oestradiol level s (P>0.05). The prostatic stromal cells, including SMCs and fibroblasts, di minished and underwent a serial pathological change of atrophy and apoptosi s after castration. The atrophic cells were filled with intracellular lipof uscin. The expression of SMC myosin declined after castration, coincident w ith the increase in TGF-beta mRNA level and decline in bFGF mRNA. In vitro, TGF-beta inhibited the growth of human prostatic stromal cells during expo nential growth, while enhancing myosin staining and stimulating the express ion of smoothelin in confluent cultured stromal cells, bFGF stimulated the growth of the culture and inhibited the expression of smoothelin, DHT cause d a weak increase in the proliferation and expression of SMC-specific prote ins (P<0.05). However, DHT and bFGF together stimulated the proliferation o f stromal cells significantly more than either agent alone (P<0.01). The co mbination of DHT and TGF-beta greatly enhanced the expression of SMC-specif ic proteins (P<0.01), more strongly than either alone (P<0.01). Conclusions The whole prostate gland is an androgen-sensitive organ, with b oth the epithelium and stroma under the control of androgen. Androgen may d irect the proliferation and differentiation of prostatic stromal cells by r egulating the expression of TGF-beta and bFGF. Thus DHT, TGF-beta and bFGF may have important roles in regulating stromal cell homeostasis.