Skip to main content
SpringerLink
Log in

Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone

  • Published:
Osteoporosis International Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafs-son J-A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93:5925–30.

    Google Scholar 

  2. Smith DF, Toft DO. Steroid receptors and their associated proteins. Mol Endocrinol 1993;7:4–11.

    Google Scholar 

  3. Beekman JM, Allan GF, Tsai SY, Tsai M-J, O'Malley BW. Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain. Mol Endocrinol 1993;7:1266–74.

    Google Scholar 

  4. McDonnell DP, Nawaz Z, O'Malley BW. In situ distinction between steroid receptor binding and transactivation at a target gene. Mol Cell Biol 1991;11:4350–5.

    Google Scholar 

  5. Kumar V, Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell 1988;55:145–56.

    Google Scholar 

  6. Ing N, Beekman J, Tsai S, Tsai M-J, O'Malley B. Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). J Biol Chem 1992;267:17617–23.

    Google Scholar 

  7. Onate SA, Tsai S, Tsai M-J, O'Malley BW. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 1995;270:1354–7.

    Google Scholar 

  8. Halachmi S, Marden E, Martin G, MacKay H, Abbondanza C, Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science 1944;264:1455–8.

    Google Scholar 

  9. Cavaillès V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J 1995;14:3741–51.

    Google Scholar 

  10. Elliston J, Fawell S, Klein-Hitpass L, Tsai S, Tsai M-J, Parker M, O'Malley B. Mechanism of estrogen receptor-dependent transcription in a cell-free system. Mol Cell Biol 1990;10:6607–12.

    Google Scholar 

  11. Klein-Hitpass L, Tsai SY, Weigel NL, Allan GF, Riley D, Rodriguez R, Schrader WT, Tsai M-J, O'Malley BW. The progesterone receptor stimulates cell-free transcription by enhancing the formation of a stable preinitiation complex. Cell 1990;60:247–257.

    Google Scholar 

  12. Gottardis MM, Robinson SP, Jordan VC. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic nude mice: a model to study the tumoristatic action of tamoxifen. J Steroid Biochem 1988;30:311–4.

    Google Scholar 

  13. Love RR, Wiebe DA, Newcombe PA, Cameron L, Leventhal H, Jordan VC, et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Intern Med 1991;115:860–4.

    Google Scholar 

  14. Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992;326:852–6.

    Google Scholar 

  15. Jordan VC. The strategic use of antiestrogens to control the development and growth of breast cancer. Cancer 1992;70:977–82.

    Google Scholar 

  16. McDonnell DP, Lieberman BA, Norris J. Development of tissue-selective estrogen receptor modulators. In: Baird DT, Schutz G, Krattenmacher R (ed) Organ-selective actions of steroid hormones, vol 16. Berlin: Springer, 1995:1–28.

    Google Scholar 

  17. McDonnell DP, Clemm DL, Herman T, Goldman ME, Pike JW. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol 1995;9:659–69.

    Google Scholar 

  18. Draper MW, Flowers DE, Huster WJ, Neild JA. Effects of raloxifene (LY 139481 HCL) on biochemical markers of bone and lipid metabolism in healthy postmenopausal women. Aalborg: Handelstrykkeriet, 1993

    Google Scholar 

  19. Yang NN, Bryant HU, Hardikar S, Sato M, Galvin RJS, Glasebrook AL, Termine JD. Estrogen and raloxifene stimulate transforming growth factor-63 gene expression in rat bone: potential mechanism for estrogen-or raloxifene mediated bone maintenance. Endocrinology 1996;137:2075–84.

    Google Scholar 

  20. Katzenellenbogen JA, O'Malley BW, Katzenellenbogen BS. Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell-and promoter-specific action of these hormones. Mol Endocrinol 1996;10:119–31.

    Google Scholar 

  21. Clark JH, Peck EJ. Female sex steroids: receptors and function, vol 14. Berlin: Springer, 1979.

    Google Scholar 

  22. Tzukerman MT, Esty A, Santiso-Mere D, Danielian P, Parker MG, Stein RB et al. Human estrogen receptor transcriptional capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol 1994;8:21–30.

    Google Scholar 

  23. Meyer ME, Pornon A, Ji J, Bocquel MT, Chambon P, Gronemeyer H. Agonist and antagonist properties of RU486 on the functions of the human progesterone receptor. EMBO J 1990;9:3923–32.

    Google Scholar 

  24. Webb P, Lopez GN, Uht RM, Kushner PJ. Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol 1995;9:443–56.

    Google Scholar 

  25. Gibson MK, Nemmers LA, Beckman WCJ, Davis VL, Curtis SW, Korach KS. The mechanism of ICI 164,384 antiestrogenicity involves rapid loss of estrogen receptor in uterine tissue. Endocrinology 1991;129:2000–10.

    Google Scholar 

  26. Mahfoudi A, Roulet E, Dauvois S, Parker MG, Wahli W. Specific mutations in the estrogen receptor change the properties of antiestrogens to full agonists. Proc Natl Acad Sci USA 1995;92:4206–10.

    Google Scholar 

  27. Wrenn CK, Katzenellenbogen BS. Structure-function analysis of the hormone binding domain of the human estrogen receptor by region-specific mutagenesis and phenotypic screening in yeast. J Biol Chem 1993;268:24089–98.

    Google Scholar 

  28. Norris J, Fan D, Aleman C, Marks JR, Futreal A, Wiseman RW, et al. Identification of a new subclass of alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J Biol Chem 1995;270:22777–82.

    Google Scholar 

  29. McDonnell DP, Clemm DL, Imhof MO. Definition of the cellular mechanisms which distinguish between hormone and antihormone activated steroid receptors. Semin in Cancer Biol 1994;5:503–13.

    Google Scholar 

  30. Danielian PS, White R, Lees JA, Parker MG. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J 1992;11:1025–33.

    Google Scholar 

  31. Norris J, Fan D and McDonnell DP. Identification of the sequences within the human complement 3 promoter required for estrogen responsiveness provides insight into the mechanism of taxoxifen mixed agonist activity. Molecular Endocrinology 1996;10:1605–1616.

    Google Scholar 

  32. Chen HK, Ke HZ, Ma YF, Crawford DT, Pirie CM, Simmons HA, et al. Droloxifene inhibits cortical bone turnover associated with estrogen deficiency in rats. Bone 1995;17:175–9.

    Google Scholar 

  33. Willson TM, Henke BR, Momtahen TM, Charifson PS, Batchelor KW, Lubahn DB, Moore LB, Oliver BB, Sauls HR and Triantafillou JA. 3-[4-(1,2-Diphenylbut-1-enyl-phenyl]acrylic acid: a non-steroidal estrogen with functional selectivity for bone over uterus in rats. J Med Chem 1994;37:1550–1552.

    Google Scholar 

  34. Chow J, Thobias JH, Colston KW, Chambers TJ. Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation. J Clin Invest 1992;89:74–8.

    Google Scholar 

  35. Dukes M, Chester R, Yarwood L, Wakeling AE. Effects of a non-steroidal pure antiestrogen, ZM 189,154, on oestrogen target organs of the rat including bones. J Endocrinol 1994;141:335–41.

    Google Scholar 

  36. Dauvois S, Danielian PS, White R, Parker MG. Antiestrogen ICI164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc Natl Acad Sci USA 1992;89:4037–41.

    Google Scholar 

  37. Dauvois S, White R, Parker MG. The antiestrogen ICI 182,780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 1993;106:1377–88.

    Google Scholar 

  38. Parker MG. Action of “pure” antiestrogens in inhibiting estrogen receptor action. Breast Cancer Res Treat 1993;26:131–137.

    Google Scholar 

  39. Fawell SE, White R, Hoare S, Sydenham M, Page M, Parker MG. Inhibition of estrogen receptor-DNA binding by the “pure” antiestrogen ICI164,384 appears to be mediated by impaired receptor dimerization. Proc Natl Acad Sci USA 1990;87:6883–7.

    Google Scholar 

  40. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 1992;257:88–91.

    Google Scholar 

  41. Stein B, Yang M. Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kB and C/EBP6. Mol Cell Biol 1995;15:4971–9.

    Google Scholar 

  42. Ray A, Prefontaine KE, Ray P. Down-regulation of interleukin-6 gene expression by 17-β-estradiol in the absence of high affinity DNA binding by the estrogen receptor. J Biol Chem 1994 ; 269:12940–6.

    Google Scholar 

  43. Evans RM. The steroid and thyroid hormone receptor super-family. Science 1988;240:889–95.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Duke University Medical School, Box 3813, 27710, Durham, NC, USA

    D. P. McDonnell & J. D. Norris

Authors
  1. D. P. McDonnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. D. Norris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. P. McDonnell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDonnell, D.P., Norris, J.D. Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone. Osteoporosis Int 7 (Suppl 1), 29–34 (1997). https://doi.org/10.1007/BF01674810

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01674810

Keywords

Search

Navigation