GROWTH-STIMULATORY EFFECT AND METABOLISM OF TESTOSTERONE IN MCF-7 HUMAN BREAST-CANCER CELLS

The purpose of our study was to evaluate the effect of testosterone an d its metabolic pathway in MCF-7 cells in culture. Testosterone exhibi ted a dose-dependent (from 0.1 to 10 nM) and time-dependent (from 3 to 9 days) growth stimulation. The metabolic pathway was investigated fo llowing treatment with two testosterone concentrations: one stimulatin g (10 nM) and one not affecting (0.1 nM) cell growth. Celite column ch romatography was used to separate H-3-testosterone metabolites, whose identity was confirmed by gas chromatography-mass spectrometry analysi s. The main findings of the metabolic study were: i) recovery of a lar ge amount of untransformed testosterone; ii) a high conversion of test osterone to conjugated, biologically inactive metabolites; iii) the hi ghest level of Sa-diol among the metabolites of testosterone; iv) a co nversion (2%) of testosterone into oestradiol, which resulted in a gro wth stimulatory concentration when testosterone was used at 10 nM. We conclude that in our experimental conditions androgens and oestrogens can concur to stimulate MCF-7 cell growth through androgen receptor-me diated and oestrogen receptor-mediated mechanisms.