Estrogen Receptor-Cofactor Interactions as Targets for Novel Drug Discovery
The steroid hormone estrogen is a key regulator of the processes involved in cellular differentiation and proliferation. Estrogen is most notably involved in the precise neuro-endocrine control of ovulation as well as in determining secondary sexual characteristics in developing females. However, emerging evidence suggests that estrogens have much broader effects on human physiology. It is now well-established that estrogen is involved in the maintenance of skeletal integrity, triglyceride balance, and behavioral responses in both males and females (Bertelli et al. 1988; Love et al. 1992; Ogawa et al. 1997). In addition to these normal physiological actions of estrogen, the hormone has also been implicated in the development and progression of breast cancer, a disease that afflicts one in eight women. Anti-estrogens, compounds that bind to the estrogen receptor (ER) and oppose the mitogenic actions of estrogen, have therefore become frontline breast cancer therapeutics. In simplest terms, anti-estrogens work by competing for agonist binding to the ER and preventing it from becoming activated (McDonnell 1999). The first anti-estrogen developed for use as a breast cancer treatment was tamoxifen (Jordan and Murphy 1990).
KeywordsEstrogen Receptor Nuclear Receptor Partial Agonist Activity Human Estrogen Receptor Estrogen Receptor Agonist
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