Estrogen tamoxifen

Yamaguchi and Gao, 1998 Rat femoral-metaphyseal tissues cultured for 48 h with bone resorbing factors PTH, PGE2 or EPS) +/- genistein measured bone calcium content, acid and alkaline phosphatases Genistein (10 Yi O M) inhibited bone resorption. Effect reversed by anti-estrogen, tamoxifen. 

Zajchowski et al. [107] showed comparison of expression profiles between 38 different estrogen receptor-modulating compounds. An intial study was run based on the results of profiling of 24 combinations of cells and genes with estrogen, tamoxifen, raloxifene and ICI 164384 (a pure ER antagonist). Using the optimized assay panel derived from these studies, the 38 compounds were then profiled and classi-... 

Fig. 12 Chemical structures of first and second generation non-steroidal anti-estrogens (tamoxifen and derivatives), and novel third generation SERMs...

A. B. Grey, J. P. Stapleton, M. C. Evans, I. R. Reid (1995). The effect of anti-estrogen tamoxifen on cardiovascular risk factors in normal post-menopausal women. J. Clin. Endocrinol. Metab. 80 8192. 

Increased TBG Estrogens, tamoxifen, heroin, methadone, mitotane, fluorouracil... 

Tamoxifen, the antiestrogen most widely used for the treatment of breast cancer, has shown clear clinical benefits in advanced breast cancer, its efficacy being comparable with that achieved by ablative and additive therapies (Furr and Jordan, 1984) (Fig. 1). In the first clinical studies, initiated in 1969, tamoxifen was found to achieve remissions in advanced breast carcinoma similar to those observed following estrogen therapy but with fewer side effects (Cole et al., 1971). Since then, because of its favorable profile and clinical efficacy, comparable with that of other endocrine therapies, including oophorectomy and estrogens, tamoxifen has become the treatment of choice for patients with advanced or metastatic breast cancer (Buchanan et al., 1986 Howell et al, 1990 Ingle etal, 1981). 

Drug use (oral contraceptives, estrogens, tamoxifen, methadone)... 

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. 

Classic steroid receptors Estrogen receptor ERcr ER/3 NR3A1 NR3A2 Estradiol, estrogens Tamoxifen, raloxifene (Evista), genestein, diethylstilbestrol, equine estrogens (Premarin) Menopausal symptoms, osteoporosis prevention, breast cancer... 

In a typical assay, tamoxifen is used as a positive control, and this yields an antiestrogenic response with an IC50 of about 0.324 /rg/ml (575nM). In addition, as with other cell lines, cytotoxicity can be assessed to establish specificity. In general, follow-up work is performed in which competitive binding is assessed with the anti-estrogen (tamoxifen) binding site (43). 

Anti-estrogens Tamoxifen, toremifene Breast cancer... 

---