SOLUBLE AND NUCLEAR TYPE-I AND TYPE-II ANDROGEN-BINDING SITES IN BENIGN HYPERPLASIA AND CANCER OF THE HUMAN PROSTATE

This paper presents an approach for the assessment of the androgen receptor (AR) status in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues. Evaluation of AR was carried out in both soluble and nuclear fractions by a standard competition method, using tritiated mibolerone as radioligand. Based on our experience with breast and endometrial cancer, this approach focused on both type I (high affinity, low capacity) and type II (reduced affinity, higher capacity) binding sites, aiming mainly at establishing a putative "functional" receptor mechanism, i.e., the presence of type I AR in both cytosol and nucleus. Ancillary studies were carried out to exclude a potential overestimation of the AR content by interference with other steroid receptors, namely, progesterone (PgR) or glucocorticoid (GcR) receptors. Results showed that the interaction by PgR or GcR upon AR measurement was not relevant. The distribution of AR, namely the percent of positivity either in a single or in both cell compartments, was not significantly different in BPH (N = 32) or PCa (N = 24) tissues. For type I binding, the percent of positivity in both soluble and nuclear fractions (i.e., the "functional" AR status) was very close to that observed for other endocrine-related tumors, like breast cancer. Concentrations of type I AR appeared significantly higher in PCa than in BPH tissues: this was true for both soluble and nuclear fractions. In contrast, no significant difference was found in type II AR concentrations in either cell fraction. Nuclear type I AR proved to be positive in the great majority (more than 90%) of both PCa and BPH specimens: thus, this study does not support the hypothesis that nuclear AR may have a prognostic value, as previously suggested. Until long-term follow-up data on PCa patients are available, the predictive value of AR status, as estimated by this approach, cannot bc assessed; however, in parallel with the studies carried out on estrogen receptor status in breast cancer patients, we suggest that a "functional" AR status is better indicated by the presence of type I binding in both cell fractions.