The steroid receptor superfamily comprises the glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), androgen (AR), thyroid hormone (TR),and vitamin D3 (VDR) receptors (60). These receptors bind to steroid hormones and are translocated to the nucleus where they bind to hormone responsive elements on DNApromotor regions to alter gene expression. While steroids are very effective anti-inflammatory agents, they have a multiplicity of serious side effects that limit their full use.
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 j3-subtypes of the estrogen receptor (ERa and ERj3) 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, ta-moxifen interacts with a specific coactivator, SRC1, that is abundant in uterine tissue.
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