Metabolic Profiles of Androgens in Malignant Human Liver Cell Lines
In this study we have investigated androgen (testosterone and androstenedione) metabolism in malignant HepG2, Huh-7, and HA22T human liver cell lines. Following 72-h incubation with testosterone or androstenedione, estrogen formation through aromatase activity was consistently higher in HepG2 cells (being nearly 100%) and moderate in Huh7 cells (34%), while it was undetectable in HA22T cells. The produced estrogens are completely conjugated by estrogen sulpho-transferase (EST) in HepG2 cells, while nearly 25% remains in the free form in Huh-7 cells. The HA22T and Huh-7 cells show a markedly different balance of 5?- versus 5?-reduced androgens (65.7% vs. 2.5% and 2.6% vs. 22.2%, respectively), while no detectable 5?/5?-reduced androgen is formed in HepG2 cells. These divergent metabolic profiles, coupling aromatase to EST, and to 5?/5?-reductase, hint at a differential regulation of androgen metabolic pathways that may ultimately lead to a distinct impact of biologically active metabolites on growth and function of human liver cancer cells
est aromatase 5?-androgens hcc cells