Progesterone receptor antagonists

Nuclear Receptors as Drug Targets

Volumn 39, Issue , 2008, Pages 223-248

  Spitz, Irving M ^a  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

Author keywords

Progesterone receptor antagonists (PAs); Progesterone receptor modulators (PRMs); Selective progesterone receptor modulators (SPRMs)

Indexed keywords

PROGESTERONE RECEPTOR;

EID: 68949188645     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527623297.ch7     Document Type: Chapter

References (122)

1. Philibert, D. (1984) Adrenal Steroid Antagonism, Walter deGruyter, Berlin, pp. 77-101.
2. Winneker, R.C., Fensome, A., Wrobel, J.E., Zhang, Z. and Zhang, P. (2005) Nonsteroidal progesterone receptor modulators: structure-activity relationships. Seminars in Reproductive Medicine, 23, 46-57.
3. Wiechert, R. and Neef, G. (1987) Synthesis of antiprogestational steroids. Journal of Steroid Biochemistry, 27, 851-858.
4. Elger, W., Fahnrich, M., Beier, S., Qing, S.S. and Chwalisz, K. (1987) Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs. American Journal of Obstetrics and Gynecology, 157, 1065-1074.
5. Klijn, J.G., Setyono Han, B. and Foekens, J.A. (2000) Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. Steroids, 65, 825-830.
6. Fuhrmann, U., Hess-Stumpp, H., Cleve, A., Neef, G., Schwede, W., Hoffmann, J., Fritzemeier, K.H. and Chwalisz, K. (2000) Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. Journal of Medicinal Chemistry, 43, 5010-5016.
7. Slayden, O.D., Chwalisz, K. and Brenner, R.M. (2001) Reversible suppression of menstruation with progesterone antagonists in rhesus macaques. Human Reproduction, 16, 1562-1574.
8. Heikinheimo, O., Vani, S., Carpen, O., Harkki, P., Tapper, A., Rutanen, E.M. and Critchley, H. (2007) SGI Annual Scientific Meeting, Reno, NV.
9. DeManno, D., Elger, W., Garg, R., Lee, R., Schneider, B., Hess-Stumpp, H., Schubert, G. and Chwalisz, K. (2003) Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids, 68, 1019-1032.
10. Elger, W., Bartley, J., Schneider, B., Kaufmann, G., Schubert, G. and Chwalisz, K. (2000) Endocrine pharmacological characterization of progesterone antagonists and progesterone receptor modulators with respect to PR-agonistic and antagonistic activity. Steroids, 65, 713-723.
11. Chwalisz, K., Perez, M.C., Demanno, D., Winkel, C., Schubert, G. and Elger, W. (2005) Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocrine Reviews, 26, 423-438.
12. Kloosterboer, H.J., Deckers, G.H., Schoonen, W.G., Hanssen, R.G., Rose, U.M., Verbost, P.M., Hsiu, J.G., Williams, R.F. and Hodgen, G.D. (2000) Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids, 65, 733-740.
13. Gainer, E.E. and Ulmann, A. (2003) Pharmacologic properties of CDB(VA)-2914. Steroids, 68, 1005-1011.
14. Giangrande, P.H. and McDonnell, D.P. (1999) The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. Recent Progress in Hormone Research, 54, 291-313; discussion, 313-314.
15. Kastner, P., Krust, A., Turcotte, B., Stropp, U., Tora, L., Gronemeyer, H. and Chambon, P. (1990) Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO Journal, 9, 1603-1614.
16. Wei, L.L., Hawkins, P., Baker, C., Norris, B., Sheridan, P.L. and Quinn, P.G. (1996) An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity. Molecular Endocrinology, 10, 1379-1387.
17. Condon, J.C., Hardy, D.B., Kovaric, K. and Mendelson, C.R. (2006) Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-κB may contribute to the onset of labor through inhibition of PR function. Molecular Endocrinology, 20, 764-775.
18. Mulac-Jericevic, B. and Conneely, O.M. (2004) Reproductive tissue selective actions of progesterone receptors. Reproduction, 128, 139-146.
19. Vegeto, E., Allan, G.F., Schrader, W.T., Tsai, M.J., McDonnell, D.P. and O'Malley, B.W. (1992) The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell, 69, 703-713.
20. Smith, C.L. and O'Malley, B.W. (2004) Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocrine Reviews, 25, 45-71.
21. Wagner, B.L., Norris, J.D., Knotts, T.A., Weigel, N.L. and McDonnell, D.P. (1998) The nuclear corepressors NCoR and SMRT are key regulators of both ligand and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Molecular and Cellular Biology, 18, 1369-1378.
22. Bray, J.D., Grygielko, E.T., Sulpizio, A.C., Pullen, M.A., Haimbach, R.E., Gu, J.L., Wu, C. and Laping, N.J. (2006) Endocrine Society Meeting, Boston, MA.
23. Spitz, I.M. and Bardin, C.W., (1993) Mifepristone (RU 486) - a modulator of progestin and glucocorticoid action. New England Journal ofMedicine, 329, 404-412.
24. Johannisson, E., Oberholzer, M., Swahn, M.L. and Bygdeman, M. (1989) Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486. Contraception, 39, 103-117.
25. Garfield, R.E., Blennerhassett, M.G. and Miller, S.M. (1988) Control of myometrial contractility: role and regulation of gap junctions. Oxford Reviews in Reproductive Biology, 10, 436-490.
26. Bygdeman, M. and Swahn, M.L. (1985) Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception, 32, 45-51.
27. Cheng, L., Kelly, R.W., Thong, K.J., Hume, R. and Baird, D.T. (1993) The effects of mifepristone (RU486) on prostagland in dehydrogenase in decidual and chorionic tissue in early pregnancy. Human Reproduction, 8, 705-709.
28. Cheng, L., Kelly, R.W., Thong, K.J., Hume, R. and Baird, D.T. (1993) The effect of mifepristone (RU486) on the immunohistochemical distribution of prostagland in E and its metabolite in decidual and chorionic tissue in early pregnancy. Journal of Clinical Endocrinology and Metabolism, 77, 873-877.
29. Chwalisz, K. and Garfield, R.E. (1998) New molecular challenges in the induction on cervical ripening. Human Reproduction, 13, 245-252.
30. Vaisanen-Tommiska, M., Butzow, R., Ylikorkala, O. and Mikkola, T.S. (2006) Mifepristone-induced nitric oxide release and expression of nitric oxide synthases in the human cervix during early pregnancy. Human Reproduction, 21, 2180-2184.
31. Hodgen, G.D., van Uem, J.F., Chillik, C.F., Danforth, D.R., Wolf, J.P., Neulen, J., Williams, R.F. and Chwalisz, K. (1994) Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models. Human Reproduction, 9 (Suppl 1), 77-81.
32. Chwalisz, K., Brenner, R.M., Fuhrmann, U.U., Hess Stumpp, H. and Elger, W. (2000) Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids, 65, 741-751.
33. Neulen, J., Williams, R.F., Breckwoldt, M., Chwalisz, K., Baulieu, E.E. and Hodgen, G.D. (1996) Non-competitive anti-oestrogenic actions of progesterone antagonists in primate endometrium:enhancement of oestrogen and progesterone receptors with blockade of post-receptor proliferative mechanisms. Human Reproduction, 11, 1533-1537.
34. Slayden, O.D. and Brenner, R.M. (1994) RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatta). Journal of Clinical Endocrinology and Metabolism, 78, 440-448.
35. Brenner, R.M., Slayden, O.D. and Critchley, H.O. (2002) Anti-proliferative effects of progesterone antagonists in the primate endometrium: a potential role for the androgen receptor. Reproduction, 124, 167-172.
36. Slayden, O.D., Zelinski-Wooten, M.B., Chwalisz, K., Stouffer, R.L. and Brenner, R.M. (1998) Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct. Human Reproduction, 13, 269-277.
37. Slayden, O.D., Carroll, R., Mah, K. and Brenner, R.M. (2006) SGI 53rd Annual Meeting, Toronto, Ontario.
38. Slayden, O.D. and Brenner, R.M. (2003) Flutamide counteracts the antiproliferative effects of antiprogestins in the primate endometrium. Journal of Clinical Endocrinology and Metabolism, 88, 946-949.
39. McDonnell, D.P. and Goldman, M.E. (1994) RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism. Journal of Biological Chemistry, 269, 11945-11949.
40. Zelinski Wooten, M.B., Slayden, O.D., Chwalisz, K., Hess, D.L., Brenner, R.M. and Stouffer, R.L. (1998) Chronic treatment of female rhesus monkeys with low doses of the antiprogestinZK137 316:establishment of a regimen that permits normal menstrual cyclicity. Human Reproduction, 13, 259-267.
41. Koji, T., Chedid, M., Rubin, J.S., Slayden, O.D., Csaky, K.G., Aaronson, S.A. and Brenner, R.M. (1994) Progesteronedependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: keratinocyte growth factor as a progestomedin. Journal of Cell Biology, 125, 393-401.
42. Grow, D.R., Reece, M.T., Hsiu, J.G., Adams, L., Newcomb, P.M., Williams, R.F. and Hodgen, G.D. (1998) Chronic antiprogestin therapy produces a stable atrophic endometrium with decreased fibroblast growth factor: a 1-year primate study on contraception and amenorrhea. Fertility and Sterility, 69, 936-943.
43. Greb, R.R., Heikinheimo, O., Williams, R.F., Hodgen, G.D. and Goodman, A.L. (1997) Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesteronereceptor ligands in vivo. Human Reproduction, 12, 1280-1292.
44. Heikinheimo, O., Hsiu, J.G., Gordon, K., Kim, S., Williams, R.F., Gibbons, W.E. and Hodgen, G.D. (1996) Endometrial effects of RU486 in primates - antiproliferative action despite signs of estrogen action and increased cyclin-B expression. Journal of Steroid Biochemistry and Molecular Biology, 59, 179-190.
45. Parthasarathy, S., Morales, A.J. and Murphy, A.A. (1994) Antioxidant: a new role for RU-486 and related compounds. Journal of Clinical Investigation, 94, 1990-1995.
46. Li, A., Felix, J.C., Minoo, P., Amezcua, C.A. and Jain, J.K. (2005) Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells. Fertility and Sterility, 84, 202-211.
47. Narvekar, N., Critchley, H.O., Cheng, L. and Baird, D.T. (2006) Mifepristoneinduced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor. Human Reproduction, 21, 2312-2318.
48. Shoupe, D., Mishell, D.R., Jr. Page, M.A., Madkour, H., Spitz, I.M. and Lobo, R.A. (1987) Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase. American Journal of Obstetrics and Gynecology, 157, 1421-1426.
49. Cameron, S.T., Critchley, H.O., Thong, K.J., Buckley, C.H., Williams, A.R. and Baird, D.T. (1996) Effects of daily low dose mifepristone on endometrial maturation and proliferation. Human Reproduction, 11, 2518-2526.
50. Chwalisz, K., Elger, W., Stickler, T., Mattia-Goldberg, C. and Larsen, L. (2005) The effects of one-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in normal women. Human Reproduction, 20, 1090-1099.
51. Chwalisz, K., Garg, R., Brenner, R.M., Schubert, G. and Elger, W. (2002) Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept in endometriosis. Annals of the New York Academy of Sciences, 955, 373-388.
52. Christin-Maitre, S., Bouchard, P. and Spitz, I.M. (2000) Medical termination of pregnancy. New England Journal of Medicine, 342, 946-956.
53. Fiala, C. and Gemzel-Danielsson, K. (2006) Review of medical abortion using mifepristone in combination with a prostagland in analogue. Contraception, 74, 66-86.
54. Fischer, M., Bhatnagar, J., Guarner, J., Reagan, S., Hacker, J.K., Van Meter, S.H., Poukens, V., Whiteman, D.B., Iton, A., Cheung, M., Dassey, D.E., Shieh, W.J. and Zaki, S.R. (2005) Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. New England Journal of Medicine, 353, 2352-2360.
55. Sinave, C., Le Templier, G., Blouin, D., Leveille, F. and Deland, E. (2002) Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease. Clinical Infectious Diseases, 35, 1441-1443.
56. Laue, L., Lotze, M.T., Chrousos, G.P., Barnes, K., Loriaux, D.L. and Fleisher, T.A. (1990) Effect of chronic treatment with the glucocorticoid antagonistRU486 in man: toxicity, immunological, and hormonal aspects. Journal of Clinical Endocrinology and Metabolism, 71, 1474-1480.
57. Heikinheimo, O., Raivio, T., Honkanen, H., Ranta, S. and Janne, O.A. (2003) Termination of pregnancy with mifepristone and prostagland in suppresses transiently circulating glucocorticoid bioactivity. Journal of Clinical Endocrinology and Metabolism, 88, 323-326.
58. Laue, L., Kawai, S., Brandon, D.D., Brightwell, D., Barnes, K., Knazek, R.A., Loriaux, D.L. and Chrousos, G.P. (1988) Receptor-mediated effects of glucocorticoids on inflammation:enhancement of the inflammatory response with a glucocorticoid antagonist. Journal of Steroid Biochemistry, 29, 591-598.
59. Spitz, I.M., Grunberg, S., Chabbert-Buffet, N., Lindenberg, T., Gelber, H. and Sitruk-Ware, R. (2005) Management of patients receiving long term treatment with mifepristone. Fertility and Sterility, 84, 1719-1726.
60. van der Schoot, P. (1992) Treatment with mifepristone (RU486) and oestradiol facilitates the development of genital septic disease after copulation in female rats. Human Reproduction, 7, 601-605.
61. Cabrol, D., Dubois, C., Cronje, H., Gonnet, J.M., Guillot, M., Maria, B., Moodley, J., Oury, J.F., Thoulon, J.M., Treisser, A., Ulmann, D., Correl, S. and Ulmann, A. (1990) Induction of labor with mifepristone (RU 486) in intrauterine fetal death. American Journal of Obstetrics and Gynecology, 163, 540-542.
62. Wagaarachchi, P.T., Ashok, P.W., Narvekar, N.N., Smith, N.C. and Templeton, A. (2002) Medical management of late intrauterine death using a combination of mifepristone and misoprostol. British Journal of Obstetrics and Gynaecology, 109, 443-447.
63. WorldHealth Organization Task Force on Postovulatory Methods of Fertility Regulation, Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. (1999) Lancet, 353, 697-702.
64. Xiao, B.L., von Hertzen, H., Zhao, H. and Piaggio, G. (2002) A randomized doubleblind comparison of two single doses of mifepristone for emergency contraception. Human Reproduction, 17, 3084-3089.
65. von Hertzen, H., Piaggio, G., Ding, J., Chen, J., Song, S., Bartfai, G., Ng, E., Gemzell Danielsson, K., Oyunbileg, A., Wu, S., Cheng, W., Ludicke, F., Pretnar Darovec, A., Kirkman, R., Mittal, S., Khomassuridze, A., Apter, D. and Peregoudov, A. (2002) Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet, 360, 1803-1810.
66. Creinin, M.D., Schlaff, W., Archer, D.F., Wan, L., Frezieres, R., Thomas, M., Rosenberg, M. and Higgins, J. (2006) Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstetrics and Gynecology, 108, 1089-1097.
67. Gronlund, A., Gronlund, L., Clevin, L., Andersen, B., Palmgren, N. and Lidegaard, O. (2002) Management of missed abortion: comparison of medical treatment with either mifepristone + misoprostol or misoprostol alone with surgical evacuation. Amulti-center trial in Copenhagen county, Denmark. Acta Obstetrica et Gynecologica Scandinavica, 81, 1060-1065.
68. Goldberg, A.B., Greenberg, M.B. and Darney, P.D. (2001) Misoprostol and pregnancy. New England Journal of Medicine, 344, 38-47.
69. Steinauer, J., Pritts, E.A., Jackson, R. and Jacoby, A.F. (2004) Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstetrics and Gynecology, 103, 1331-1336.
70. Eisinger, S.H., Bonfiglio, T., Fiscella, K., Meldrum, S. and Guzick, D.S. (2005) Twelve-month safety and efficacy of lowdose mifepristone for uterine myomas. Journal of Minimally Invasive Gynecology, 12, 227-233.
71. Eisinger, S.H., Meldrum, S., Fiscella, K., le Roux, H.D. and Guzick, D.S. (2003) Low-dose mifepristone for uterine leiomyomata. Obstetrics and Gynecology, 101, 243-250.
72. Fiscella, K., Eisinger, S.H., Meldrum, S., Feng, C., Fisher, S.G. and Guzick, D.S. (2006) Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial. Obstetrics and Gynecology, 108, 1381-1387.
73. Chwalisz, K., Larsen, L., Mattia-Goldberg, C., Edmonds, A., Elger, W. and Winkel, C.A. (2007) Arandomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata. Fertility and Sterility, 62, 662-663.
74. Kettel, L.M., Murphy, A.A., Morales, A.J., Rivier, J., Vale, W. and Yen, S.S. (1993) Rapid regression of uterine leiomyomas in response to daily administration of gonadotropin-releasing hormone antagonist. Fertility and Sterility, 60, 642-646.
75. Kettel, L.M., Murphy, A.A., Morales, A.J., Ulmann, A., Baulieu, E.E. and Yen, S.S. (1996) Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertility and Sterility, 65, 23-28.
76. Kettel, L.M., Murphy, A.A., Morales, A.J. and Yen, S.S. (1998) Preliminary report on the treatment of endometriosis with lowdose mifepristone (RU 486). American Journal of Obstetrics and Gynecology, 178, 1151-1156.
77. Chwalisz, K., Mattia-Goldberg, K., Lee, M., Elger, W. and Edmonds, A. (2004) Treatment of endometriosis with the novel selective progesterone receptor modulator (SPRM) asoprisnil. Fertility and Sterility, 82, S83.
78. Broekmans, F.J. (1996) GnRH agonists and uterine leiomyomas. Human Reproduction, 11, (Suppl 3) 3-25.
79. Yen, S.S.C. (1993) Use of antiprogestins in the management of endometriosis and leiomyoma, in Clinical Applications of Mifepristone (RU496) and Other Antiprogestins, (eds M.S. Donaldson, L. Dorflinger, S.S. Brown and L.Z. Benet), National Academy Press, Washington, DC, pp. 189-209.
80. Brown, A., Cheng, L., Lin, S. and Baird, D.T. (2002) Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation:a double-blind randomized control trial of 2 and 5mg per day for 120 days. Journal of Clinical Endocrinology and Metabolism, 87, 63-70.
81. Croxatto, H.B., Salvatierra, A.M., Fuentealba, B. and Massai, R. (1998) Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women. Human Reproduction, 13, 3297-3302.
82. Massai, R., Forcelledo, M.L., Quinteros, E., Fuentealba, B. and Croxatto, H. (2003) Anticoncepcion oral libre de estrogenos:regimen secuencial antiprogestina-progestina. Cuban Journal of Public Health, 29, R104.
83. Gemzell Danielsson, K., Swahn, M.L., Svalander, P. and Bygdeman, M. (1993) Early luteal phase treatment with mifepristone (RU 486) for fertility regulation. Human Reproduction, 8, 870-873.
84. Hapangama, D.K., Brown, A., Glasier, A.F. and Baird, D.T. (2001) Feasibility of administering mifepristone as a once a month contraceptive pill. Human Reproduction, 16, 1145-1150.
85. Chen, X. and Xiao, B. (1997) Effect of once weekly administration of mifepristone on ovarian function in normal women. Contraception, 56, 175-180.
86. Pei, K., Xiao, B., Jing, X., Lu, S., Wei, L. and Zhao, H. (2007) Weekly contraception with mifepristone. Contraception, 75, 40-44.
87. Cheng, L., Zhu, H., Wang, A., Ren, F., Chen, J. and Glasier, A. (2000) Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel. Human Reproduction, 15, 1969-1972.
88. Massai, M.R., Pavez, M., Fuentealba, B., Croxatto, H.B. and d'Arcangues, C. (2004) Effect of intermittent treatment with mifepristone on bleeding patterns, in Norplant implant users. Contraception, 70, 47-54.
89. Jain, J.K., Nicosia, A.F., Nucatola, D.L., Lu, J.J., Kuo, J. and Felix, J.C. (2003) Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate. Steroids, 68, 1115-1119.
90. Weisberg, E., Hickey, M., Palmer, D., O'Connor, V., Salamonsen, L.A., Findlay, J.K. and Fraser, I.S. (2006) Apilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon. Human Reproduction, 21, 295-302.
91. Verbost, P.M., Hanssen, R.G.J.M., Korver, G.H.V. and Mulders, T.M.T. (2005) ORG 33628 and ORG 31710 control vaginal bleeding in progestin-only contraceptive regimens. Seminars in Reproductive Medicine, 23, 101-111.
92. Messinis, I.E., Krishnan, M., Kazem, R., Khadilkar, S. and Templeton, A.A. (1997) Effect of mifepristone on folliculogenesis in women treated with, recombinant FSH. Clinical Endocrinology (Oxford), 46, 309-314.
93. Escudero, E.L., Boerrigter, P.J., Bennink, H.J., Epifanio, R., Horcajadas, J.A., Olivennes, F., Pellicer, A. and Simon, C. (2005) Mifepristone is an effective oral alternative for the prevention of premature luteinizing hormone surges and/or premature luteinization in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Journal of Clinical Endocrinology and Metabolism, 90, 2081-2088
94. Hegele Hartung, C., Mootz, U. and Beier, H.M. (1992) Luteal control of endometrial receptivity and its modification by progesterone antagonists. Endocrinology, 131, 2446-2460.
95. Paulson, R.J., Sauer, M.V. and Lobo, R.A. (1997) Potential enhancement of endometrial receptivity in cycles using controlled ovarian hyperstimulation with antiprogestins: a hypothesis. Fertility and Sterility, 67, 321-325.
96. Cekan, S., Aedo, A.R., Segersteen, E., Van Look, P., Messinis, I. and Templeton, A. (1989) Levels of the antiprogestin RU 486 and its metabolites in human blood and follicular fluid following oral administration of a single dose. Human Reproduction, 4, 131-135.
97. Rocereto, T.F., Saul, H.M., Aikins, J.A., Jr. and Paulson, J. (2000) Phase II study of mifepristone (RU486) in refractory ovarian cancer. Gynecologic Oncology, 77, 429-432.
98. Koivisto-Korander, R., Leminen, A. and Heikinheimo, O. (2007) Mifepristone as treatment of recurrent progesterone receptor-positive uterine leiomyosarcoma. Obstetrics and Gynecology, 109, 512-514.
99. Critchley, H., Williams, A., Cameron, I., Lumsden, M.A., Chwalisz, K., Holz, C. and Wessel, J. (2007) SGI Annual Scientific Meeting, Reno, NV.
100. Slayden, O.D., Zelinski, M.B., Chwalisz, K., Hess-Stumpp, H. and Brenner, R.M. (2006) Chronic progesterone antagonistestradiol therapy suppresses breakthrough bleeding and endometrial proliferation in a menopausal macaque model. Human Reproduction, 21, 3081-3090.
101. Grunberg, S.M., Weiss, M.H., Russell, C.A., Spitz, I.M., Ahmadi, J., Sadun, A. and Sitruk-Ware, R. (2006) Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma. Cancer Investigations, 24, 727-733.
102. Grunberg, S.M., Rankin, C., Townsend, J., Ahamadi, J., Feun, L., Fredricks, R., Russell, C.A., Kabbinavar, F., Barger, G.R. and Stelzer, K.J. (2001) American Society of Clinical Oncology Meeting, San Francisco, CA.
103. Poole, A.J., Li, Y., Kim, Y., Lin, S.C., Lee, W.H. and Lee, E.Y. (2006) Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science, 314, 1467-1470.
104. Spitz, I.M. (2003) Progesterone antagonists and progesterone receptor modulators: an overview. Steroids, 68, 981-993.
105. Nieman, L.K., Chrousos, G.P., Kellner, C., Spitz, I.M., Nisula, B.C., Cutler, G.B., Merriam, G.R., Bardin, C.W. and Loriaux, D.L. (1985) Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. Journal of Clinical Endocrinology and Metabolism, 61, 536-540.
106. DeBattista, C. and Belanoff, J. (2006) The use of mifepristone in the treatment of neuropsychiatric disorders. Trends in Endocrinology and Metabolism, 17, 117-121.
107. Nielsen, J.S., Weinreb, R.N., Yannuzzi, L. and Jampol, L.M. (2007) Mifepristone treatment of chronic central serous chorioretinopathy. Retina, 27, 119-122.
108. Wang, X.J., Liefer, K.M., Tsai, S., O'Malley, B.W. and Roop, D.R. (1999) Development of gene-switch transgenic mice that inducibly express transforming growth factor β1 in the epidermis. Proceedings of the National Academy of Sciences of the United States, of America, 96, 8483-8488.
109. Nordstrom, J.L. (2003) The antiprogestindependent GeneSwitch system for regulated gene therapy. Steroids, 68, 1085-1094.
110. Smith, L.C. and Nordstrom, J.L. (2000) Advances in plasmid gene delivery and expression in skeletal muscle. Current Opinion in Molecular Therapeutics, 2, 150-154.
111. Arnett-Mansfield, R.L., DeFazio, A., Mote, P.A. and Clarke, C.L. (2004) Subnuclear distribution of progesterone receptors A and B in normal and malignant endometrium. Journal of Clinical Endocrinology and Metabolism, 89, 1429-1442.
112. McGowan, E.M., Saad, S., Bendall, L.J., Bradstock, K.F. and Clarke, C.L. (2004) Effect of progesterone receptor α predominance on breast cancer cell migration into bone marrow fibroblasts. Breast Cancer Research and Treatment, 83, 211-220.
113. Berrodin, T.J., Jelinsky, S.A., Graciani, N., Winneker, R.C. and Yudt, M.R. (2006) Endocrine Society Meeting, Boston, MA.
114. Fuhrmann, U. (2006) 12th international Congress on Hormonal Steroids and Hormones & Cancer, Athens.
115. Heikinheimo, O., Ranta, S., Grunberg, S., Lahteenmaki, P. and Spitz, I.M. (1997) Alterations in the pituitary-thyroid and pituitary-adrenal axes - consequences of long-term mifepristone treatment. Metabolism: Clinical and Experimental, 46, 292-296.
116. Fleischer, A.C., Wheeler, J.E., Yeh, I.T., Kravitz, B., Jensen, C. and MacDonald, B. (1999) Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene. Journal of Ultrasound and Medicine, 18, 503-512.
117. Liedman, R., Lindahl, B., Andolf, E., Willen, R., Ingvar, C. and Ranstam, J. (2000) Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Research, 20, 4889-4891.
118. Baird, D.T., Brown, A., Critchley, H.O., Williams, A.R., Lin, S. and Cheng, L. (2003) Effect of long-term treatment with lowdose mifepristone on the endometrium. Human Reproduction, 18, 61-68.
119. Newfield, R.S., Spitz, I.M., Isacson, C. and New, M.I. (2001) Long-term mifepristone (RU486) therapy resulting in massive benign, endometrial hyperplasia. Clinical Endocrinology (Oxford) 54, 399-404.
120. Horne, F.M. and Blithe, D.L. (2007) Progesterone receptor modulators and the endometrium: changes and consequences. Human Reproduction Update, 13, 567-580.
121. Williams, A.R., Critchley, H.O., Osei, J., Ingamells, S., Cameron, I.T., Han, C. and Chwalisz, K. (2007) The effects of the selective progesterone receptor modulator asoprisnil on the morphology of uterine tissues after 3 months treatment in patients with symptomatic uterine leiomyomata. Human Reproduction, 22, 1696-1704.
122. Narvekar, N., Cameron, S., Critchley, H.O., Lin, S., Cheng, L. and Baird, D.T. (2004) Low-dose mifepristone inhibits endometrial proliferation and upregulates androgens receptor. Journal of Clinical Endocrinology and Metabolism, 89, 2491-2497.