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Raloxifene: A selective estrogen receptor modulator

  • Supplement 2: Estrogen And Anti-Estrogen
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Raloxifene is a benzothiophene derivative that was first examined ten years ago and has variously been referred to as keoxifene, LY139431, or LY156758. Raloxifene was classified generally as an anti-estrogen, because like tamoxifen it antagonizes the stiimulatory effects of estrogen on uterine weight. However, raloxifene inhibited the proliferation of the human breast cancer cell line, MCF-7, with IC50=0.2 nM compared to IC50=200 nM for tamoxifen; and histological analysis of uteri from ovariectomized rats showed that raloxifene does not significantly affect epithelial cell height or induce eosinophilia as tamoxifen does. At other sites, raloxifene has estrogen and tamoxifen-like effects on bone and serum cholesterol levels in ovariectomized rats. At 5 weeks, ovariectomy induced a 9% and 18% decrease in the bone mineral density of the lumbar vertebrae L1-4 and proximal tibiae, respectively. Raloxifene prevented this loss of bone with EC50=0.3 mg/kg/day for both the axial and appendicular skeleton. The bone effects of raloxifene could not be distinguished from estrogen effects, at the respective maximally efficacious doses. Raloxifene also lowered serum cholesterol levels to below Sham with ED50=0.2 mg/kg/day, in a manner similar to estrogen and tamoxifen. These data show that raloxifene has tissue specific effects that are distinct from either estrogen or tamoxifen. With breast tissue and uteri, raloxifene functions as a complete estrogen antagonist; but in bone and serum lipids, it behaves as a potent estrogen agonist. Because of this unique pharmmacological profile, we have classified raloxifene as a “selective estrogen receptor modulator (SERM).” We also note that the data taken together suggests that raloxifene may have tissue selective properties that may be advantageous to clinicians treating post-menopausal osteoporosis.

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Authors and Affiliations

  1. MC 797, Department of Endocrine Research, Lilly Corporate Center Indianapolis, 46285, IN, USA

    Masahiko Sato, Andrew L. Glasebrook & Henry U. Bryant

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  1. Masahiko Sato
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  2. Andrew L. Glasebrook
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  3. Henry U. Bryant
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Sato, M., Glasebrook, A.L. & Bryant, H.U. Raloxifene: A selective estrogen receptor modulator. J Bone Miner Metab 12 (Suppl 2), S9–S20 (1994). https://doi.org/10.1007/BF02383389

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  • DOI: https://doi.org/10.1007/BF02383389

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