Agonistic and antagonistic effects of antiestrogens in different target organs.

Antiestrogens block by definition specifically the actions of estrogens. In the classical uterotropic assay in immature rodents, where estrogens cause fluid retention and cell proliferation, triphenylethylenes have also species-specific estrogen-like (agonistic) effects. 4-hydroxylated triphenylethylenes have in general less estrogenic properties than unhydroxylated ones, and ICI 164,384 has no estrogenic activity in this model. Uterus responds to estrogens by stimulation of cell proliferation. Some other tissues, like breast, liver, and bone respond by regulation of specific protein synthesis. Some of the proteins act as growth factors, and some have unknown functions. The regulation of gene expression is a complex phenomenon: estrogens may turn the responsive gene on or off. Similarly antiestrogens may participate in the gene regulation by mimicking or antagonising estrogen-like actions. This paper summarizes the estrogenic and antiestrogenic effects of classical and new antiestrogens in different tissues.