Effect of Mestranol on Cell Proliferation and Angiotensinogen Production in HepG2 Cells: Relation with the Cell Cycle and Action of Tamoxifen

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Abstract
The effects of the estrogen analog mestranol and of the antiestrogen tamoxifen on cell growth and the rate of angiotensinogen production were investigated in HepG2 cells, an hepato-carcinoma cell line of human origin. After 36 h of cell contact with high concentration of mestranol, a (10-5 M) dose increased by 2-fold the rate of proliferation of HepG2 while reducing angiotensinogen production to below control level. Mestranol at 10-6 M preferentially stimulated angiotensinogen production 5-fold, whereas cell growth rate was slightly increased. Comparable results were obtained for thymidine uptake in the course of the cell cycle, with a maximum increase for 10-5 M mestranol, and an increase of angiotensinogen production for 10-6 M mestranol. At 10-6 M, tamoxifen acted as a pure antagonist by strongly inhibiting the stimulatory effect of mestranol and reducing angiotensinogen production to below the control level within 60 h. Tamoxifen did not affect the growth rate of HepG2 cells, either when administered alone or together with an equimolar concentration of mestranol.