The Department of Medicine, University of Toronto, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada
Abstract:
Studies using 3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by Cortisol (10?6 M) and inhibited by endogenous 5-reduced androgens: 5-androstene-dione>androsterone>dihydrotestosterone>epiandrosterone>3- and 3β-androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10?6 M) inhibited E1 formation by 80%. Progesterone (10?6 M) had no effect on aromatase activity, while the progestational agent R5020 (10?6 M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action.