Tamoxifen tissue-selectivity

Somjen D, Waisman A, Kaye AM (1996) Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo. J Steroid Biochem Mol Biol 59(5-6) 389-396... 

There also exist a class of ligands referred to as SERMs (selective estrogen receptor modulators) that display tissue-selective pharmacology [13]. Raloxifene and tamoxifen are two clinically used SERMs for which structures are available. Crystal structures of the estrogen receptor bound to different ligands (estradiol, tamoxifen, or raloxifene) reveal that ligands of different sizes and shapes induce a spectrum of receptor conformational states. These states can be interpreted by the cellular complexion of co-regulators and the environment of the local promoter of... 

The anti-estrogen, tamoxifen, is the most commonly used hormonal therapy for breast cancer and has demonstrated positive effects on the cardiovascular and skeletal systems of postmenopausal women but is associated with an increased risk of uterine cancer. Tamoxifen is described as a SERM, a selective estrogen receptor modulator with a tissue selective profile that is caused by the different distribution of the a- and /3-subtypes of the estrogen receptor (ERa and ER/3) that activate and inhibit transcription respectively (77). These selective effects have been ascribed to differential interactions with gene promotor elements and coregulatory proteins depending on whether the ERa interacts directly, or in a tethered manner with DNA (78). In uterine tissue, tamoxifen interacts with a specific coactivator, SRCl, that is abundant in uterine tissue. 

SELECTIVE ESTROGEN RECEPTOR MODULATORS AND ANTIESTROGENS SERMs TAMOXIFEN, RALOXIFENE, AND TOREMIFENE Selective ER modulators, or SERMs, exert tissue-selective actions. Their pharmacological goal is to produce beneficial estrogenic actions in certain tissues (e.g., bone, brain, and Uver) but antagonist activity in others... 

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