Heterogeneity of Binding Sites for Triphenylethylene Antiestrogens in Estrogen Target Tissues
Most of the interest in understanding the mechanism of action of triphenylethylene antiestrogens (Fig. 1) arises from their ability to induce weak estrogenic effects, to antagonize many of the actions of estrogens and to induce the remission of human breast cancer particularly during the post-menopausal period (Legha et al., 1978). In particular, these compounds are able to suppress estrogen-induced uterine growth (Jordan et al., 1977) and to antagonize estrogen-induced growth of human breast cancer cells which contain estrogen receptor (Lippman et al., 1976). In this regard, triphenylethylene antiestrogens are used for understanding the mechanism by which estrogens regulate cell growth. However, triphenylethylene antiestrogens are also able to inhibit the growth of estrogen sensitive and estrogen receptor containing human breast cancer cells, even in the absence of estrogens (Lippman et al., 1976). The attempt to understand the mechanism of action of both estrogen and antiestrogens awaits the elucidation of the molecular events and interactions which occur at the subcellular and cellular level. In recent years, multiple interactions of triphenylethylene antiestrogens have been reported at the subcellular level: a) the interaction with the estrogen receptor system (Terenius, 1971; Lippman et al., 1976; Horwitz and McGuire, 1978), and b) the binding of these compounds to specific binding sites distinct from the estrogen receptor in several experimental models such as the chick oviduct (Sutherland and Foo, 1979), rat uterus (Faye et al., 1980), fetal guinea pig uterus (Gulino and Pasqualini, 1980), human mammary cancer (Sutherland and Murphy, 1980) and human myometrium (Kon, 1983). The aim of this paper is to summarize the data so far known about the interactions of triphenylethylene antiestrogens with target cells at the subcellular level.
KeywordsEstrogen Cortisol Sedimentation Testosterone Progesterone
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