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Body weight, uteri, serum cholesterol and bones were shown previously in vivo to be sensitive to circulating levels of estrogen, as well as to synthetic, nonsteroidal ligands termed selective estrogen receptor modulators (SERM). In this study, we examined the in vivo effects of a new potent SERM on these tissues in 6-month-old, ovariectomized rats that were orally dosed with 0.0001-10 mg/kg/day...

CONTEXT Tamoxifen has been approved for breast cancer risk reduction in high-risk women, but how raloxifene compares with tamoxifen is unknown. OBJECTIVE To compare the differences in patient-reported outcomes, quality of life [QOL], and symptoms in Study of Tamoxifen and Raloxifene (STAR) participants by treatment assignment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS STAR was a doub...

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or ant...

Amino acid Asp-351 in the ligand binding domain of estrogen receptor (ER ) plays an important role in regulating the estrogen-like activity of selective estrogen receptor modulator-ER complexes. 4-Hydroxytamoxifen is a full agonist at a transforming growth factor target gene in situ in MDA-MB-231 human breast cancer cells stably transfected with the wild-type ER . In contrast, raloxifene (Ral),...

Cancer can be described as the uncontrolled growth of abnormal cells. Breast cancer is the second most common type of cancer after lung cancer. Normal breast cells and most breast cancer cells have receptors that attach to circulating estrogen and progesterone. Estrogen and progesterone bind to the receptors and may work with growth factors (e.g., oncogenes and mutated tumor suppressor genes) t...

PURPOSE To assess the effect of raloxifene, indicated for osteoporosis treatment and prevention, on invasive breast cancer in subgroups of postmenopausal women defined by risk factors for breast cancer. EXPERIMENTAL DESIGN Data from the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial (N=7,705) and a follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial...

Estrogens and selective estrogen receptor modulators (SERMs) interact with estrogen receptor (ER) and to activate or repress gene transcription. To understand how estrogens and SERMs exert tissue-specific effects, we performed microarray analysis to determine whether ER or ER regulate different target genes in response to estrogens and SERMs. We prepared human U2OS osteosarcoma cells that are s...

In early discovery, compounds are often eliminated because of their potential to undergo metabolic activation and/or cytochrome P450 time-dependent inactivation (TDI). The blockbuster drug raloxifene is an example of a compound that would have been eliminated in the current paradigm. Despite raloxifene's in vitro bioactivation and TDI of CYP3A4, it is well tolerated in patients with no drug-dru...

OBJECTIVE To study the effect of raloxifene on endometrial histopathology of menopausal women. METHODS Thirty-one patients under raloxifene treatment (60 mg/day) for a six-month period and submitted to diagnostic videohysteroscopy at the Climateric Outpatients Clinic, Department of Gynecology and Obstetrics, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, in the city of Sã...