Proliferation and differentiation of prostatic stromal cells.

Abstract

To investigate the effects of androgen, transforming growth factor beta1 (TGF-beta) and basic fibroblast growth factor (bFGF) on the proliferation and differentiation of prostatic stromal cells of the dog in vivo and human stromal cells in vitro. Twenty-two dogs had their serum concentration of testosterone and oestradiol determined by radioimmunoassay before and after castration. 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 transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the expression of TGF-beta, bFGF and myosin in the canine prostate tissue after castration. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT), TGF-beta and bFGF in various concentrations. The proliferation of the cell cultures was detected by the tetrazolium assay. The differentiation from fibroblasts to smooth muscle cells (SMCs) was deduced by measuring the expression of SMC-specific proteins (myosin and smoothelin) using immunohistochemistry and RT-PCR. Castration resulted in a significant decrease in circulating testosterone levels (P < 0.01), but did not affect the circulating oestradiol levels (P > 0.05). The prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent a serial pathological change of atrophy and apoptosis after castration. The atrophic cells were filled with intracellular lipofuscin. The expression of SMC myosin declined after castration, coincident with 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 exponential growth, while enhancing myosin staining and stimulating the expression of smoothelin in confluent cultured stromal cells. bFGF stimulated the growth of the culture and inhibited the expression of smoothelin. 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 TGF-beta greatly enhanced the expression of SMC-specific proteins (P < 0.01), more strongly than either alone (P < 0.01). 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 and differentiation of prostatic stromal cells by regulating the expression of TGF-beta and bFGF. Thus DHT, TGF-beta and bFGF may have important roles in regulating stromal cell homeostasis.