Androgens (testosterone and its metabolites) play a large role in the normal growth and function of the prostate. However, changes in androgen metabolism or responsiveness to androgens have been implicated in the formation of benign prostatic hypertrophy and prostate cancer. The causes of these changes are not well understood. Studies were undertaken to determine what if any differences in androgen metabolism occur between androgen dependent and androgen independent prostate cancer cells. Whole cell studies showed that in androgen dependent cells, added testosterone is primarily glucuronidated. The cellular level of total testosterone, i.e. testosterone plus its glucuronide, remain constant during the entire incubation period. The kinetics, regulation, and physiologic effect of glucuronidation is being investigated. Androgen- independent cells, on the other hand, metabolize testosterone predominantly to androsterone. Unlike the dependent cell line, very little androgen remains within the independent cell at the end of the incubation period. Assays in a cell-free system show that androgen dependent cells have high activity of UDP-glucaronyl transferase whereas enzyme activity is undetectable in androgen independent cells. We are characterizing the expression of UDP-glucuronyl transferase mRNA in these cells at the RNA and protein levels. Since this enzyme is sensitive to regulation by dietary factors, we are studying the mechanisms responsible for these differences in androgen metabolism to link androgen responsiveness in the prostate to dietary factors in cancer prevention.
