ABSTRACT
Antiestrogens are compounds that act by inhibiting the action of estrogen on target cells. The first ones described, such as ethamoxytriphetol (MER-25) and clomiphene (MRL-41, chloramiphene) (Lerner et al., 1958; Holtkamp et al., 1960) were discovered by their ability to inhibit estrogen-induced biological endpoints. This was before the first description of estrogen receptors as the modulators of estrogen action, and long before the recent discovery of the presence of two estrogen receptor subtypes. Recent evidence suggests that estrogen receptor α (ERα) and ERβ signal in different ways from an API enhancer element when complexed with estradiol, ERα activating and ERβ inhibiting transcription. All antiestrogens tested induced transcription, although in different degrees, at the ERα-AP1 site and also, unlike estrogens, at the ERβ-AP1 site (Paech et al., 1997). Such differences in ligand-induced transactivation may explain differential biological activity of selective estrogen receptor modulators (SERMs).
