Development of Tissue-Selective Estrogen Receptor Modulators

  • D. P. McDonnell
  • B. A. Lieberman
  • J. Norris
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 16)


The steroid hormone estrogen is a key intracellular modulator of the processes involved in differentiation, homeostasis, and development of female reproductive function (Clark and Peck 1979). In pathological states, estrogen is also involved in the maintenance and progression of cancers (Sunderland and Osborne 1991) and is implicated in the abnormalities of uterine function observed in endometriosis and possibly uterine fibroids (Kettel et al. 1991). The pharmaceutical exploitation of the estrogen receptor (ER) has seen the development of antihormones, compounds which can oppose the function of the natural hormone estrogen (Kedar et al. 1994; Sunderland and Osborne 1991). One such compound, tamoxifen, has found widespread use in the clinic as adjuvant hormonal therapy for breast cancer where it functions as an antagonist of those estrogen-regulated genes responsible for cellular proliferation (Kedar et al. 1994; Sunderland and Osborne 1991). Interestingly, in bone and in the cardiovascular system, tamoxifen exhibits sufficient ER agonist activity to maintain bone mass and cardiovascular tone in postmenopausal women (Love et al. 1992). Because of these favorable activities, along with its breast-selective antagonist activities, tamoxifen is currently being evaluated as a chemopreventative agent in patients who are at high risk for developing breast cancer (Henderson et al. 1993). Unfortunately, its utility for this application may be adversely affected according to a recent study which indicated that 37% of women taking tamoxifen demonstrated histological changes in the endometrium indicative of unopposed ER agonist activity (Kedar et al. 1994).


Estrogen Receptor Human Estrogen Receptor Estrogen Receptor Agonist Estrogen Receptor Ligand Pure Antiestrogen 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • D. P. McDonnell
  • B. A. Lieberman
  • J. Norris

There are no affiliations available

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