Differential effects of estramustine phosphate upon cell proliferation in mouse accessory sex glands

The effects of estramustine phosphate (EMP) have been measured during the proliferative response of the seminal vesicle and coagulating gland of the castrated mouse after continuous treatment with testosterone. Daily subcutaneous injections of 60 micrograms testosterone were begun 14 days after castration. Three daily injections of EMP (100 mg/kg body wt) were begun on either day 11 or day 13 after castration. Cell proliferation was monitored by [3H]thymidine-labelling techniques combined with autoradiography, and by determinations of mitotic index. Treatment with EMP on days 11, 12 and 13 after castration almost completely blocked the testosterone-induced proliferative response in the coagulating gland. Treatment with EMP commencing on day 13 after castration was less effective. Estramustine phosphate had a small stimulatory effect on DNA synthesis and mitosis in the seminal vesicle. Measurements of 5 alpha-reductase activity in vitro did not reflect the dynamic cell kinetic changes observed in both tissues in vivo. We have concluded that previous assay systems using the Coffey model are unsuitable for the assessment of antiandrogens and prostatic anti-cancer drugs.