Urokinase-type plasminogen activator is increased in the involuting ventral prostate of castrated rats

We have investigated the content of plasminogen activators in the rat ventral prostate during castration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography demonstrated two major Mr-forms of plasminogen activators that were found to be strongly increased by castration; inclusion of quenching antibodies in the zymography and immunoblotting analysis identified these as urokinase-type plasminogen activator (u-PA) and its Mr 30,000 degradation product, respectively. A third, less abundant form, which was identified as tissue-type plasminogen activator, was also increased by castration. The induction of the plasminogen activators was prevented by treating the rats with 5 alpha-dihydrotestosterone. The increase in u-PA antigen was quantitated by the use of enzyme-linked immunosorbent assay. The increases in u-PA activity and antigen were traced back to a corresponding increase in u-PA messenger RNA (mRNA). By immunohistochemical methods, the u-PA was found to be present in scattered single cells at the surface of the epithelium facing the lumen of the glandular ducts. Such cells were present in control as well as in castrated rats, but their number increased after castration. In addition, after castration, u-PA immunoreactivity appeared in cells throughout the epithelium. These results suggest a role for plasminogen activation in castration-induced involution of the rat ventral prostate, and a role in the normal turnover of the rat ventral prostate epithelium.