The metabolism of androstenedione and testosterone to C 19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue

Abstract

In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C 19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C 19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C 19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5α-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5β-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5α reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.