Pharmacodynamic and biological effects of anti-estrogens in different models.

The biological response to anti-estrogens is very variable and depends on the animal species considered, the target organ, the parameter studied, and the experimental conditions. Anti-estrogens can bind specifically, (1) to the estrogen receptor, (2) to the typical anti-estrogen specific binding site, and (3) to low density lipoproteins in the plasma. Using a monoclonal antibody against the estrogen receptor, different immunological characteristics of the anti-estrogen-receptor complex can be observed. This difference could explain some of the different biological effects. Studies using different human mammary cancer cell lines (hormone-dependent) show that anti-estrogens are active in decreasing cell proliferation. Also, anti-estrogens can block proteins specifically produced by these cells. Some of these proteins could act as growth or inhibitory factors. Estrogen sulfates are the main precursors of estradiol in breast tissues and this conversion is significantly decreased by anti-estrogens. It is accepted that the main pathway of action of anti-estrogens is through the estrogen receptor, but recent information suggests the possibility that this is not the only step in the mechanism of action of anti-estrogens.