An estrogen receptor basis for raloxifene action in bone

Journal of Steroid Biochemistry and Molecular Biology

Volumn 69, Issue 1-6, 1999, Pages 37-44

  Bryant, Henry U ^a   Glasebrook, Andrew L ^a   Yang, Na N ^a   Sato, Masahiko ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Estrogen receptor; Raloxifene; SERM

Indexed keywords

BENZOTHIOPHENE DERIVATIVE; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CHOLESTEROL; DNA; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; INTERLEUKIN 6; MESSENGER RNA; RALOXIFENE; TAMOXIFEN; TRANSFORMING GROWTH FACTOR BETA3;

BINDING AFFINITY; BONE; BONE DENSITY; BONE GROWTH; BONE MINERAL; BONE TURNOVER; CARDIOVASCULAR SYSTEM; CHOLESTEROL METABOLISM; CONFERENCE PAPER; CRYSTAL STRUCTURE; DRUG RECEPTOR BINDING; DUAL ENERGY X RAY ABSORPTIOMETRY; HUMAN; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; BONE AND BONES; ESTROGEN ANTAGONISTS; ESTROGENS; PIPERIDINES; RALOXIFENE; RECEPTORS, ESTROGEN;

EID: 0032976913     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-0760(98)00147-2     Document Type: Conference Paper

References (34)

1. Kumar V., Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand induced homodimer. Cell. 55:1988;145-156.
2. Krishnan V., Wang X., Safe S. Estrogen receptor Spl complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 cells. J. Biol. Chem. 269:1994;15912-15917.
3. Yang N.N., Venugopalan M., Glasebrook A.L. Identification of an estrogen response element activated by metabolites of 17β-estradiol and raloxifene. Science. 273:1996;1222-1225.
4. McDonnel D.P., Clemm D.L., Hermann T., Goldman M.E., Pike J.W. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol. Endocrinol. 9:1995;659-669.
5. Kauffman R.F., Bryant H.U. Selective estrogen receptor modulators. Drug News Perspect. 8:1995;531-539.
6. Black L.J., Sato M., Rowley E.R., Magee D.E., Bekele A., Williams D.C., Cullinan G.J., Bendele R., Kauffman R.F., Bensch W.R., Frolik C.A., Termine J.D., Bryant H.U. Raloxifene (LY139481 HCl) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J. Clin. Invest. 93:1994;63-69.
7. Jerome C.P., Lees C.J., Registar T.C., Stancill M. Iliac and lumbar vertebral histomopometry, bone densitometry and bone biomarker data from raloxifene-treated macaques. J. Bone Mineral Res. 12 (Suppl. 1):1997;S347.
8. Delmas P.D., Bjarnason N.H., Mitlak B.H., Ravoux A.-C., Shah A.S., Huster W.J., Draper M., Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. New Engl. J. Med. 337:1997;1641-1647.
9. Bryant H.U., Wilson P.K., Adrian M.D., Cole H.W., Phillips D.L., Dodge J.A., Grese T.A., Sluka J.P., Glasebrook A.L. Selective estrogen receptor modulators: pharmacological profile in the rat uterus. J. Soc. Gynecol. Invest. 3:1996;152A.
10. Glasebrook A.L., Phillips D.L., Sluka J.P. Multiple binding sites for the antiestrogen raloxifene. J. Bone Mineral Res. 8 (Suppl. 1):1993;S268.
11. Gize E.A., Venugopalan M., Glasebrook A.L., Yang N.N. Characterization of raloxifene binding and transactivation properties of the estrogen receptor-beta. J. Bone Mineral Res. 12 (Suppl. 1):1997;S428.
12. Brzozowski A.M., Pike A.C.W., Dauler Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.-A., Garlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 389:1997;753-758.
13. Kauffman R.F., Bensch W.R., Roudebush R.E., Cole H.W., Bean J.S., Phillips D., Monroe A., Cullinan G.J., Glasebrook A.L., Bryant H.U. Hypocholesterolemic activity of raloxifene (LY139481): Pharmacological characterization as a selective estrogen receptor modulator (SERM). J. Pharmacol. Exp. Ther. 280:1997;146-153.
14. Turner R.T., Rigs B.L., Spelsberg T.C. Skeletal effects of estrogen. Endocrine Rev. 15:1994;275-300.
15. Evans G., Bryant H.U., Magee D., Sato M., Turner R.T. The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology. 134:1994;2283-2288.
16. Sato M., McClintock C., Kim J., Turner C., Bryant H.U., Magee D.E., Slemenda C.W. Dual-energy X-ray absorptiometry of raloxifene effects on the lumbar vertebrae and femora of ovariectomized rats. J. Bone Mineral Res. 9:1994;715-724.
17. Sato M., Kim J., Short L.L., Slemenda C.W., Bryant H.U. Longitudinal and cross-sectional analysis of raloxifene effects on tibiae from ovariectomized aged rats. J. Pharmacol. Exp. Ther. 272:1995;1252-1259.
18. Turner C.H., Sato M., Bryant H.U. Raloxifene preserves bone strength and bone mass in ovariectomized rats. Endocrinology. 135:1994;2001-2005.
19. Bryant H.U., Turner C.H., Frolik C.A., Magee D.E., Cole H.W., Brown C.E., Rippy M.K., Sato M. Long term effects of raloxifene (LY139478 HCl) on bone, cholesterol and uterus in ovariectomized rats. Bone. 16 (Suppl.):1995;116S.
20. Bryant H.U., Cole H.W., Adrian M.D., Wilson P.K., Sato M. Raloxifene and estrogen preserve PTH induced bone mass in ovariectomized rats. FASEB J. 10:1996;A469.
21. Jiang Y., Zhao J., Van Audekercke R., Dequeker J., Geusens P. Effects of low dose long term sodium fluoride preventative treatment on rat bone mass and biomechanical properties. Calcif. Tissue Int. 58:1996;30-39.
22. Dempster D.W., Cosman F., Parisien M., Shen V., Lindsay R. Anabolic actions of parathyroid hormone on bone. Endocrine Rev. 14:1993;690-709.
23. Evans G., Magee D., Bryant H.U., Turner R.T. Raloxifene is as effective as estrogen in preventing further bone loss in mature rats with established bone loss. Endocrinology. 137:1996;4139-4144.
24. Frolik C.A., Bryant H.U., Black E.C., Magee D.E., Chandrasekhar S. Time dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen and alendronate. Bone. 18:1996;621-627.
25. Bryant H.U., Magee D.E., Cole H.W., Chandrasekhar S., Hsuing H.M., Heiman M.L., Sato M. Beneficial effects of ethynyl estradiol and raloxifene in the ovariectomized rat are dependent on an intact pituitary. J. Bone Mineral Res. 9 (Suppl. 1):1994;S135.
26. Magee D.E., Cole H.W., Brown C.E., Bryant H.U. Raloxifene and estrogen retain antiosteopenic activity in ovariectomized rats fed a low calcium diet. J. Bone Mineral Res. 9 (Suppl. 1):1994;S198.
27. Bryant H.U., Black L.J., Rowley E.R., Sato M., Cullinan G.J. Medroxyprogesterone augments the bone effects of estrogen or raloxifene in the ovariectomized rat. Endocr. Soc. Abstr. 77:1995;597.
28. Shetler P.K., Rowley E.R., Cole H.W., Adrian M.D., Magee D.E., Pell T., Sato M., Bryant H.U. Raloxifene, estrogen, LY117018 and testosterone in the steroid hormone deficient male rat. J. Bone Mineral Res. 11 (Suppl. 1):1996;S446.
29. Jilka R.L., Hangoi G., Girasole G., Passeri G., Williams D.C., Abrams J.S., Boyce B., Broxmeyer H., Manolagas S.C. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. 257:1992;88-91.
30. M. Sato, H.U. Bryant, Raloxifene efficacy in nonreproductive and reproductive tissues in rat models in vivo and in vitro. in: H. Kuramoto, E. Gurpide (Eds.), In Vitro Biology of Sex Steroid Hormone Action, Churchill Livingstone, Tokyo, 1996, pp. 406-421.
31. Glasebrook A.L., Short L.L., Cole H.W., Sato M., Bryant H.U. Regulation of serum IL-6 by raloxifene in an ovariectomized rat model. Bone. 19 (Suppl. 1):1995;99S.
32. Yang N.N., Hardikar S., Sato M., Galvin R.J.S., Glasebrook A.L., Bryant H.U., Termine J.D. Estrogen and raloxifene stimulate transforming growth Factor-β3 expression in rat bone: a potential mechanism for estrogen or raloxifene-mediated bone maintenance. Endocrinology. 137:1996;275-2084.
33. Fuchs-Young R., Magee D.E., Cole H.W., Short L., Glasebrook A.L., Rippy M.K., Termine J.D., Bryant H.U. Raloxifene is a tissue-specific antiestrogen that blocks tamoxifen or estrogen-stimulated uterotrophic effects. Endocr. Soc. Abstr. 0:1995;57.
34. Grese T.A., Sluka J.P., Bryant H.U., Cole H.W., Kim J.R., Magee D.E., Rowley E.R., Sato M. Benzopyran selective estrogen receptor modulators (SERMs): pharmacological effects and structural correlation with raloxifene. Biorog. Med. Chem. Lett. 6:1996;903-908.