Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.

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We evaluated the parameters of preoperative pressure-flow for predicting the postoperative voiding difficulties in women with stress urinary incontinence. The preoperative urodynamic study records of 14 women treated using the tension-free vaginal tape (TVT) procedure were retrospectively analyzed. Of the patients treated with the TVT procedure, urinary retention occurred in one patient, and three had a residual urine volume of more than 30 ml. All patients became completely free of stress urinary incontinence postoperatively. The lowest Pdet max (5 cmH(2)O) in the preoperative pressure-flow study was found in a patient with a remarkable postoperative residual urine volume of more than 50 ml. The second lowest Pdet max value (8 cmH(2)O) was seen in a patient with postoperative urinary retention, whose residual urine volume, however, decreased to almost zero 1 year after the operation. The preoperative Pdet max x Qave values were remarkably low for these three patients, including the one with the lowest Pdet max, with a post-void residual urine volume of more than 30 ml. The plots of Pdet max x Qave versus the age of patients show that the Pdet max x Qave values tend to decrease with aging. The preoperative Pdet max x Qave value can be an important parameter for predicting increased residual urine after TVT sling surgery.

Although some anti-estrogens have been reported to inhibit the proliferation of prostate cancer cells, few studies on the mechanism by which they suppress the growth of prostate cancer have been reported. We investigated, for the first time, whether anti-estrogens modulate the transactivation activity of the androgen receptor (AR) in prostate cancer cells. In DU-145 cells transfected with AR, the transactivation activity of AR was inhibited by tamoxifen and toremifene, even in the presence of 10 nM of DHT. On the other hand, in LNCaP cells having an endogenous AR mutation at codon 877, the activity of AR was suppressed by faslodex in the presence of 10 nM DHT, whereas it was not inhibited by tamoxifen nor toremifene. In PC-3 cells, both the cell growth and the AR activity were remarkably inhibited by tamoxifen at 50 microM. Faslodex and toremifene inhibited AR activity to some extent, but they seemed to function as agonists at higher concentrations. In PC-3 cells, the inhibition of cell growth by flutamide, faslodex and toremifene was much less than their suppression of AR activity. We also demonstrated that a synthetic estrogen diethylstilbestrol and progesterone-related drugs such as chlormadinone acetate and allylestrenol dose-dependently inhibited the activity of AR in DU-145 and PC-3 cells. These results highlight the anti-androgenic aspect of anti-estrogens and estrogens in regard to the AR-mediated transcription of the relevant genes in prostate cancer.