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Antiprogestins: Past, Present, and Future

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Estrogens, Progestins, and Their Antagonists

Part of the book series: Hormones in Health and Disease ((HHD))

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Abstract

Within the last decade major breakthroughs in hormone research were achieved through the discovery of new classes of pharmacological agents, the estrogen and progesterone receptor antagonists. The progesterone antagonists are of use in two important areas of research. These compounds can be used as: (1) pharmacological probes to investigate the cellular and molecular actions of progestins, and (2) clinical agents that inhibit events regulated by estrogen and progestin. This chapter addresses the most recent research, uses, and concerns related to progesterone receptor antagonists and considers the newest antiprogestin ligands.

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References

  • Bakker GH, Setyono-Han B, Protengen H, De Jong FH, Foekens JA, Klijn M (1990): Treatment of breast cancer with different anti-progestins: Preclinical and clinical studies. J Steroid Biochem Mol Biol 37:789–794.

    Article  PubMed  CAS  Google Scholar 

  • Bakker GH, Setyono-Han B, Protengen H, de Jong FH, Foekens JA, Klijn JGM (1989): Endocrine and antitumor effects of combined treatment with an antiprogestin and antiestrogen or luteinizing hormone release hormone agonist in female rats bearing mammary tumors. Endocrinol 125:1593–1598.

    Article  CAS  Google Scholar 

  • Bakker GH, Setyono-Han B, de Jong FH, Klijn JGM (1987): Mifepristone in treatment of experimental breast cancer in rats. In: Klijn JGM, Paridaens R, Foekens JA (eds.), Hormonal Manipulation of Cancer: Peptides, Growth Factors and New (Andi-) Steroidal Agents. New York: Raven Press, pp. 39–48.

    Google Scholar 

  • Bargmann W, Fleischhauer K, Knopp A (1960): über die Morphologie der Milchsekretion. II. Zellforsch 53:545–568.

    Google Scholar 

  • Bargmann W, Welsch W (1969): On the ultrastructure of the mammary gland. In: Reynolds M, Folley SJ (eds.), Lactogenes. Philadelphia: University of Pennsylvania Press, pp. 43–52.

    Google Scholar 

  • Baulieu EE (1985a): RU 486: An antiprogestin steroid with contragestive activity in women. In: Baulieu EE, Segal SJ (eds.), The Antiprogestin Steroid RU 486 and Human Fertility Control. New York and London: Plenum Press, pp. 47–52.

    Google Scholar 

  • Baulieu EE (1985b): RU486—A decade on, today and tomorrow. In: Donaldson MS, Dorflinger L, Brown SS, Benet LZ (eds.), Clinical Applications of Mifepristone RU 486 and Other Antiprogestins, Washington: National Academy Press, pp. 71–119.

    Google Scholar 

  • Bertagna X, Bertagna C, Laudat MH, Husson JM, Girard F, Luton JP (1986): Pituitary-adrenal response to the antiglucocorticoid action of RU 486 in Cushing’s syndrome. J Clin Endocrinol Metab 63:639–643.

    Article  PubMed  CAS  Google Scholar 

  • Bigsby RM, Cunha GR (1988): Progesterone and dexamethasone inhibition of uterine epithelial proliferation in two models of estrogen-independent growth. Am J Obstet Gynecol 518:646–650.

    Google Scholar 

  • Bogden AE (1978): Therapy in experimental breast cancer models. In: McGuire WL (ed.), Breast Cancer. New York: Plenum Press, Vol. 2, pp. 283–336.

    Google Scholar 

  • Bowden TR, Hissom JR, Moore MR (1989): Growth stimulation of T47D human breast cancer cells by the antiprogestin RU 486. Endocrinol 124:2642–2646.

    Article  CAS  Google Scholar 

  • Brunner N, Bronzert D, Vindelov L, Rygaard K, Spang-Thomsen M, Lippman ME (1989): Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice. Cancer Res 49:1515–1520.

    PubMed  CAS  Google Scholar 

  • Chwalisz K, Hegele-Hartung C, Fritzemeier KH, Beier HM, Elger W (1991): Inhibition of the estradiol-mediated endometrial gland formation by the antigestagen Onapristone in rabbits: Relationship to uterine estrogen receptors. Endocrinol 129:312–322.

    Article  CAS  Google Scholar 

  • Clark GM, Dressler LG, Owens MA, Pounds G, Oldaker T, McGuire WL (1989): Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med 320:627–633.

    Article  PubMed  CAS  Google Scholar 

  • Colletta AA, Wakefield LM, Howell A, van Roozendaal KE, Danielpour D, Ebbs SR, Sporn MB, Baum M (1992): Anti-estrogens induce the secretion of active transforming growth factor-beta from fetal fibroblasts. Br J Cancer 62:405–409.

    Article  Google Scholar 

  • Crombie DL, Mukherjee R, McDonnel DP, Hayes JS, Wang MW (1994): Creatine kinase activity as an indicator of unopposed estrogen action in the mouse uterus associated with anti-progesterone treatment. J Steroid Biochem Mol Biol 49:123–129.

    Article  PubMed  CAS  Google Scholar 

  • Delabre K, Guiochon-Mantel A, Milgrom E (1993): In vivo evidence against the existence of antiprogestins distributing receptor binding to DNA. Proc Natl Acad Sci USA 90:3050–3054.

    Article  Google Scholar 

  • Donath J, Michna H, Nishino Y (1995): The antiovulatory effect of the antiprogestin Onapristone could be related to down-regulation of (intra) ovarian progesterone (receptors). J Steroid Biochem Mol Biol (In Press).

    Google Scholar 

  • Elger W, Beier S, Chwalisz K, Fähnrich M, Hasan SH, Laurent D, Beier S, Ottow E, Neef G, Garfield RE (1990): Studies on labor-conditioning and labor-inducing effects of antiprogesterones in animal models. In: Garfield RE (ed.), Uterine Contractility: Mechanisms of Control Norwell, MA: Serono Symposia, pp. 87–96.

    Google Scholar 

  • Elger W, Föhnrich M, Beier S, Shi Shao Qing J, Chwalisz K (1987): Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs. Am J Obstet Gynecol 157:1065–1074.

    PubMed  CAS  Google Scholar 

  • Garzo VG, Ulmann A, Baulieu E, Yen SSC (1988): Effects of an antiprogesterone (RU 486) on the hypothalamic-hypophyseal-ovarian-endometrial axis during the luteal phase of the menstrual cycle. J Clin Endocrinol Metab 66:508–517.

    Article  PubMed  CAS  Google Scholar 

  • Gehring S, Michna H, Khnel W, Nishino Y, Schneider MR (1991): Morphometrical and histochemical studies on the differentiation potential of progesterone antagonists in experimental mammary carcinomas. Acta Endocrinol 124:177.

    Google Scholar 

  • Gottardis MM, Jordan VC (1988): Devolopment of tamoxifen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res 48:5183–5187.

    PubMed  CAS  Google Scholar 

  • Gronemeyer H, Benhamou B, Berry M, Bocquel MT, Gofflo D, Gracia T, Leronge T, Metzger D, Meyer ME, Toral L, Vergezac A, Chambon D (1992): Mechanism of antihormone action. J Steroid Biochem Mol Biol 41:217–221.

    Article  PubMed  CAS  Google Scholar 

  • Grunberg SM, Weiss MH, Spitz M, Ahmadi J, Sadun A, Russel CA, Lucci L, Stevenson LL (1991): Treatment of unresectable meningiomas with the antiprogesterone agent Mifepristone J Neurosurg 74:861–866.

    Article  PubMed  CAS  Google Scholar 

  • Grunert G, Porcia M, Tchernitchin AN (1986): Differential potency of oestradiol-17 beta and diethylstilbestrol on seperate groups of response in the rat uterus. Endocrinol 110:103–114.

    Article  CAS  Google Scholar 

  • Hamann LG, Farmer LJ, Johnson MG, Goldmann ME, Mais DE, Davtian A, Bender SL, Jones TK (1995): Synthesis and biological activity of novel nonsteroid, progesterone receptor antagonists. In: Henderson D, Philibert D, Roy AK, Teutsch G (eds.), Steroid Receptors and Antihormones. Ann NY Acad Sci, pp. 383–388.

    Google Scholar 

  • Haslam SZ (1988): Progesterone effects on deoxyribonucleic acid synthesis in normal mouse mammary glands. Endocrinol 122:464–470.

    Article  CAS  Google Scholar 

  • Haslam SZ, Shyalama G (1981): Relative distribution of estrogen and progesterone receptors among the epithelial, adipose, and connective tissue components of the normal mammary gland. Endocrinol 108:825–830.

    Article  CAS  Google Scholar 

  • Hegele-Hartung C, Chwalisz K, Beier HM, Elger W (1989): Ripening of the uterine cervix of the guinea-pig after treatement with the progesterone antagonist Onapristone (ZK 98.299): An electron microscopic study. Hum Reprod 4:369–377.

    PubMed  CAS  Google Scholar 

  • Herman M, Bhakta A, Underwood B, Kodali S, Moudgil VK (1993): Interaction of progesterone receptor from T47D human breast cancer cells with different progestins and anti-progestins. Las Vegas: Endocrine Society, 957:290.

    Google Scholar 

  • Herrman W, Wyss R, Rinodel A, Philbert D, Teusch G, Sakiz E, Baulieu E (1982): Effect d’un steroid antiprogesterone chez la femme interruption du cycle menstruel et de la grosseesse au debut. C.R. Acad Sci 294:933–938.

    Google Scholar 

  • Horwitz KB (1992): The molecular biology of RU 486. Is there a role for antiprogestins in treatment of breast cancer? Endocrinol Rev 13(2):146–163.

    CAS  Google Scholar 

  • Horwitz KB, Takimoto GS, Tung L (1994): When steroid antagonists act like antagonists: Issues of hormone resistance and tissue specificity. In: International Congress of Hormonal Steroids, Sept. 1994, Dallas, TX.

    Google Scholar 

  • Horwitz KB (1985): The antiprogestin RU 38486: Receptor mediated progestin versus antiprogestin actions screened in estrogen-sensitive T47D10 human breast cancer cells. Endocrinol 116:2236–2245.

    Article  CAS  Google Scholar 

  • Horwitz KB, McGuire WL (1977): Progesterone and progesterone receptors in experimental breast cancer. Cancer Res 37:1733–1738.

    PubMed  CAS  Google Scholar 

  • Howell A, Dodwell DJ, Laidlaw J, Anderson H, Anderson E (1990): Tamoxifen as agonist for metastatic breast cancer. In: Goldhirsch A (ed.), Endocrine Therapy of Breast Cancer TV. Berlin: Springer Verlag, pp. 94–106.

    Google Scholar 

  • Ishwad PC, Katkam RR, Hinduja IN, Chwalisz K, Elger W, Puri CP (1993): Treatment with a progesterone antagonist ZK 98.299 delays endometrial development without blocking ovulation in bonnet monkeys. Contraception 48:1047–1057.

    Article  Google Scholar 

  • Jeng M-H, Langan-Fahey SM, Jordan, VC (1993): Estrogenic actions of RU 486 in hormone-responsive MCF-7 human breast cancer cells. Endocrinol 132:2622–2630.

    Article  CAS  Google Scholar 

  • Jeng MH, Jordan VC (1992): Estrogenic actions of RU 486 in estrogen responsive human breast cancer MCF-7 cells. Prodeedings of the 83rd Annual Meeting of the American Association for Cancer Research, San Diego, CA, pp. 282 Abstract 1684.

    Google Scholar 

  • Jonat W (1996): Clinical studies with the progesterone antagonist Onapristone in breast cancer patients. The Breast (In Press).

    Google Scholar 

  • Jo T, Terada N, Saji F, Tanizawa O (1993): Inhibitory effects of estrogen, progesterone, androgen and glucocorticoid on death of neonatal mouse uterine epithelial cells induced to proliferate by estrogen. J Steroid Biochem Mol Biol 46:25–32.

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC (1992): The role of tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer 16:134–176.

    Article  Google Scholar 

  • Kettel LM, Murphy AA, Mortola JF, Lui JH, Ulmann A, Yen SSC (1991): Endocrine responses to long-term administration of the antiprogesterone RU 486 in patients with pelvic endometriosis. Fertil Steril 56:402–407.

    PubMed  CAS  Google Scholar 

  • Klein-Hitpass L, Cato ACB, Henderson D, Ryffel GU (1991): Two types of antiprogestins identified by the differential action in transcriptionally active extracts from T47D cells. Nucleic Acids Res 1927–1234.

    Google Scholar 

  • Klein-Hitpass L, Schorpp M, Wagner U, Ryffel GU (1986): An estrogen-responsive element derived from the 5’ flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell 46:1053–1061.

    Article  PubMed  CAS  Google Scholar 

  • Klijn JAGM, de Jong FH, Bakker GH, Lamberts SWJ, Rodenburg CJ, Alexieva-Figusch J (1989): Anti-progestins, a new form of endocrine therapy for human breast cancer. Cancer Res 49:2851–2856.

    PubMed  CAS  Google Scholar 

  • Kloosterboer HJ, Deckers GH, Schoonen WGEJ (1994): Pharmacology of two new very selective anti-progestagens: Org 31710 and Org 31806. Hum Reprod 9(Suppl 1):47–52.

    PubMed  CAS  Google Scholar 

  • Kloosterboer HJ, Deckers GH, de Gooyer ME, Dijkema R, Orlemans EOM, Schoonen WGEJ (1995): Pharmacological properties of a selective anti-progestagen: Org 33682. In: Henderson D, Philibert D, Roy A, Teutsch G (eds.), Steroid Receptors and Anti-hormones. Ann NY Acad Sci, pp. 192–202.

    Google Scholar 

  • Kloosterboer HJ, Deckers GHV, Van der Heuvel MJ, Loozen HJJ (1988): Screening of antiprogestins by receptor studies and bioassays. J Steroid Biochem 31:567–571.

    Article  PubMed  CAS  Google Scholar 

  • Knabbe C, Lippmann ME, Flanders KC, Kasid A, Derynyck R, Dickson RB (1987): Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417–428.

    Article  PubMed  CAS  Google Scholar 

  • Koering MJ, Healy DL, Hodgen GD (1986): Morphologic response of endometrium to a progesterone receptor antagonist, RU 486, in monkeys. Fertil Steril 45:280–287.

    PubMed  CAS  Google Scholar 

  • Lahti E, Blanco G, Kauppila A, Apaja-Sarkkinen M, Taskinen P, Laatikainen T (1993): Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Obstet Gynecol 81:660–664.

    PubMed  CAS  Google Scholar 

  • Lamberts SWJ, Koper JW, de Jong FH (1991): The endocrine effects of long-term treatment with Mifepristone (RU 486). J Clin Endocrinol Metab 73:187–191.

    Article  PubMed  CAS  Google Scholar 

  • Ledger WL, Sweeting VM, Hiller H, Baird DT (1992): Inhibition of ovulation by low dose Mifepristone (RU 486). Human Reprod 7:945–950.

    CAS  Google Scholar 

  • Maass N, Eidmann H, Arps H, Jonat W (1994): Progesterone antagonist ZK 98.299 (Onapristone) inhibits growth of the estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer cell line MCF-7. Tumor Diagn Ther 15:6–11.

    Google Scholar 

  • Martin L (1981): Effects of antiestrogens on cell proliferation in the rodent reproductive tract. In: Sutherland RL, Jordan VC (eds.), Non-steroidal Antioestrogens. Molecular Pharmacology and Antitumor Activity. New York: Academic Press, pp. 127–135.

    Google Scholar 

  • McDonnell DP, Goldman ME (1994): RU 486 exerts antiestrogenic activities through a novel progesterone receptor A-form mediated mechanism. J Biol Chem 269(16):1945–1949.

    Google Scholar 

  • McGuire WL (1980): An update on estrogen and progesterone recptors in prognosis for primary and advanced breast cancer. In: Iacobelli F et al (eds.), Hormones and Cancer. New York: Raven Press, pp. 27–49.

    Google Scholar 

  • Meei-Huey J, Langan-Fahey SM, Jordan VC (1993): Estrogenic actions of RU 486 in hormone responsive MCF-7 human breast cancer cells. Endocrinol 132:2622–2630.

    Article  Google Scholar 

  • Michna H, Parczyk K, Schneider MR, Nishino Y (1995a): Differentiation therapy with progesterone antagonists. In: Henderson D, Philibert D, Roy A, Teutsch G (eds.), Steroid Receptors and Antihormones. New York: Ann New York Academy of Sciences, pp. 224–248.

    Google Scholar 

  • Michna H, Schneider MR, Nishino Y, El Etreby MF, McGuire WL (1990): Progesterone antagonists block the growth of experimental mammary tumors in G0G1. Breast Cancer Res Treat 17:155–156.

    Article  PubMed  CAS  Google Scholar 

  • Michna H, Parczyk K (1995): Differentiation and apoptosis as a strategy for hormone dependent cancers. In: Tenniswood M, Michna H (eds.), Apoptosis in Hormone-Dependent Cancers. Berlin: Springer, pp. 161–181.

    Google Scholar 

  • Michna H, Nishino Y, Hasan SH, Schneider MR (1993b): Morphological and endocrine reactions of hormone dependent target organs to a progesterone receptor blockade by a progesterone antagonist. Ann Anat 175:303.

    Google Scholar 

  • Michna H, Nishino Y, Schneider MR (1993c): Effective sequential treatment of experimental mammary carcinomas with tamoxifen and the progesterone antagonist Onapristone. Am Assoc Cancer Res 34:25.

    Google Scholar 

  • Michna H, Schneider MR, Nishino Y, El Etreby MF (1989a): Antitumor activity of the antiprogesterones ZK 98.299 and RU 38.486 in hormone dependent rat and mouse mammary tumors: Mechanistic studies. Breast Cancer Res Treat 14:275–288.

    Article  PubMed  CAS  Google Scholar 

  • Michna H, Schneider MR, Nishino Y, El Etreby MF (1989b): The antitumor mechanism of progesterone antagonists is a receptor mediated antiproliferative effect by induction of terminal cell death. J Steroid Biochem 34:447–453.

    Article  PubMed  CAS  Google Scholar 

  • Murphy AA, Kettel LM, Morales AJ, Roberts VJ, Yen SSC (1993): Regression of uterine leiomyomata in response to the antiprogesterone RU 486. J Clin Endocrinol Metab 76:513–517.

    Article  PubMed  CAS  Google Scholar 

  • Neef G, Beier S, Elger W, Henderson D, Wiechert R (1984): New steroids with antiprogestational and antiglucocorticoid activities. Steroids 44:349–372.

    Article  PubMed  CAS  Google Scholar 

  • Neulen J, Williams RF, Hodgen GD (1990): RU 486: Induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys. J Clin Endocrinol Metab 71:1074–1075.

    Article  PubMed  CAS  Google Scholar 

  • Neumann U, Mendoza A, Khnel W, Nishino Y, Michna H (1994): A new assay for progestins. J Steroid Biochem Mol Biol (In Press).

    Google Scholar 

  • Nishino Y, Schneider MR, Michna H (1994a): Enhancement of the antitumor efficacy of the antiprogestin, Onapristone, by combination with the antioestrogen, ICI 164.384. Eur J Cancer Clin Oncol (In Press).

    Google Scholar 

  • Nishino Y, Schubert C, Hasan S (1994b): Increase in the anti-ovulatory potency of the antiprogestin ZK 112993 by combination with the antiandrogen flutamide in the rat. Exp Clin Endocrinol 102:111.

    Article  Google Scholar 

  • Nishino Y, Michna H, Hasan SH, Schneider MR (1991): The progesterone antagonist Onapristone modulates estrogen-dependent functions in different target organs in rats and mice. Acta Endocrinol 124(Suppl 1):160.

    Google Scholar 

  • Nishino Y, Michna H, Hasan SH, Schneider MR (1992): Involvement of the adrenal gland in the prolactin rise induced in the female rat to an antiprogestin, Onapristone. J Steroid Biochem Mol Biol 41:841–845.

    Article  PubMed  CAS  Google Scholar 

  • Olson JJ, Beck DW, Schlechte JA, Loh PM (1987): Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice. J Neurosurg 66:584–587.

    Article  PubMed  CAS  Google Scholar 

  • Orlemans EOM, Deckers GH, Schoonen WGEJ, Kloosterboer HJ (1994): Pharmacology of the very selective antiprogestin Org 31710 and comparison with the antiprogestins RU 38486 and ZK 98299. Program and Abstracts, International Congress of Hormonal Steroids, Dallas, Sept. 1994.

    Google Scholar 

  • Osborne CK (1993): Mechanisms for tamoxifen resistance in breast cancer: Possible role of tamoxifen metabolism. J Steroid Biochem Mol Biol 47:83–90.

    Article  PubMed  CAS  Google Scholar 

  • Philibert D, Deraedt R, Teutsch G (1981): Ru 486: A potent antiglucocorticoiod in vivo. VHIth International Congress of Pharmacology. Toronto. Abstract 1463. congress, March 1981.

    Google Scholar 

  • Philibert D (1985): Pharmacological profile of RU 486 in animals. In: Baulieu EE, Segall SJ (eds.), The Antiprogestin Steroid RU 486 in Human Fertility Control New York: Plenum Press, pp. 49–68.

    Google Scholar 

  • Pollow K, Grill HJ, Elger W, Christmann P, Juchem M (1989): Vergleichende Untersuchungen der synthetischen Antigestagene RU 38.468, ZK 98.734 und ZK 98.299 auf Rezeptorebene. Arch Gynecol Obstet 245:929–930.

    Article  Google Scholar 

  • Rauch M, Loosfeld H, Philibert D, Milgrom E (1985): Mechanism of action of an antiprogesterone, RU 468, in the rabbit endometrium. Effects of RU 468 on the progesterone receptor and on the expression of the uteroglobin gene. Eur J Biochem 148:213–218.

    Article  PubMed  CAS  Google Scholar 

  • Reddel RR, Sutherland RL (1984): Tamoxifen stimulation of human breast cancer proliferation in vitro: A possible model for tamoxifen tumour flare. Eur J Cancer Clin Oncol 20:1419–1424.

    Article  PubMed  CAS  Google Scholar 

  • Romieu G, Maudelonde T, Ulmann A, Pujol H, Caval G, Khalaf S, Rochefort H (1987): The antiprogestin RU 486 in advanced breast cancer: Preliminary clinical trail. Bull Cancer 74:455–461.

    PubMed  CAS  Google Scholar 

  • Rumpel E, Michna H, Khnel W (1993a): Morphology of the rat uterus after long-term treatment with progesterone antagonists. Ann Anat 175:141–149.

    PubMed  CAS  Google Scholar 

  • Russo H, Russo JH (1987): Development of the human mammary gland. In: Neville MC, Daniel CW (eds.), The Mammary Gland. New York: Plenum Press, pp. 78–86.

    Google Scholar 

  • Russo JH, Medado J, Russo J (1989): Endocrine influences on the mammary glands. In: Jones TC, Mohr U, Hunt RD (eds.), Integument and Mammary Glands. Berlin: Springer Verlag.

    Google Scholar 

  • Schiaison G, George M, LeStrat N, Reinberg A, Baulieu EE (1985): Effects of the antiprogesterone steroid RU 486 during midluteal phase in normal women. J Clin Endocrinol Metab 61:484–489.

    Article  Google Scholar 

  • Schneider MR, Horn D, Michna H, Nishino Y, Vollmer G, von Angerer E (1992): Endocrine activity and tumor-inhibiting properties of the nonsteroidal pure antiestrogene ZK 119010. Acta Endocrinol (Suppl 4)126:84.

    Google Scholar 

  • Schneider MR, Michna H, Nishino Y, El Etreby MF (1989): Antitumor activity of the progesterone antagonists ZK 98299 and RU 38486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and MNU-induced mammary tumor model of the rat. Eur J Cancer Clin Oncol 25:691–701.

    Article  PubMed  CAS  Google Scholar 

  • Schubert C, Donat J, Michna H, Nishino Y (1994b): Is the antiovulatory potency of progesterone antagonists due to their antiprogestational activity? Exp Clin Endocrinol 102:91.

    Google Scholar 

  • Schubert C, Nishino Y, Michna H, Neumann F (1993): Inhibition of ovulation and the correlation to pituatary and ovarian reactions induced by the progesterone antagonist Onapristone in the rat. Exp Clin Endocrinol 101:91.

    Google Scholar 

  • Schubert C, Nishino Y, Michna H (1994a): Ovulationshemmung durch Antigestagene: Korrelation mit endokrinen und follikularen Reaktionen. Ann Anat (Suppl) 176:270.

    Google Scholar 

  • Schütt B (1993): Unpublished data.

    Google Scholar 

  • Slayden OD, Brenner RM (1994): RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatto). J Clin Endocrinol Metab 78(2):440–448.

    Article  PubMed  CAS  Google Scholar 

  • Slayden OD, Hirst JJ, Brenner RM (1993): Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment. Endocrinol 32:1845–1856.

    Article  Google Scholar 

  • Spitz IM, Bardin CV (1993): Clinical pharmacology of RU 486—An antiprogestin and antiglucocorticoid. Contraception 48:403–444.

    Article  PubMed  CAS  Google Scholar 

  • Takimoto GS, Tasset DM, Eppert AC, Horwitz KB (1992): Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: Analysis with zinc finger mutants and the progesterone antagonist ZK 98299. Proc Natl Acad Sci USA 90:4421–425.

    Google Scholar 

  • Tenniswood M, Michna H (1995): Apoptosis in Hormone-Dependent Cancers. Berlin: Springer Verlag.

    Google Scholar 

  • Terakawa N, Shimizu I, Tanizawa O, Matsumoto K (1988): RU 486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins. J Steroid Biochem 31:161–166.

    Article  PubMed  CAS  Google Scholar 

  • Teutsch G, Nique F, Lemoine G, Bouchoux F, Cerede E, Gofflo D, Philibert D (1995): General structure-activity correlations of antihormones. In: Henderson D, Philibert D, Roy A, Teutsch G (eds.), Steroid Receptors and Antihormones. New York Academy of Sciences.

    Google Scholar 

  • Teutsch G (1985): Analogues of RU 486 for the mapping of the progestin receptor: synthetic and structural aspects. In: Baulieu EE, Segal SJ (eds.), The Antiprogestin Steroid RU 486 and Human Fertility Control. New York and London: Plenum Press, pp. 212–221.

    Google Scholar 

  • Thomas M, Monet JD (1992): Combined effects of RU 486 and tamoxifen on growth and cell cycle phases of the MCF-7 cell line. J Clin Endocrinol Metab 75:865–870.

    Article  PubMed  CAS  Google Scholar 

  • Ulmann A, Peyron R, Silvestre L (1995): Clinical uses of Mifepristone. In: Henderson D, Philibert D, Roy A, Teutsch G (eds.), Steroid Receptors and Antihormones. New York Academy of Sciences.

    Google Scholar 

  • Ulmann A, Silvestre L, Chemama L, Rezvani Y, Renault M, Aguillaume J, Baulieu EE (1992): Medical termination of early pregnancy with RU486 (Mifepristone) followed by a prostaglandin analogue: Study in 16,369 women. Scand J Obstet Gynecol 71:278–283.

    Article  CAS  Google Scholar 

  • Van den Berg HW, Martin JHJ, Lynch M (1990): Progestin/anti-progestin action towards human breast cancer cell lines differing in their progesterone receptor content. Br J Pharmacol 101/Suppl.

    Google Scholar 

  • Van den Berg HW, Lynch M, Martin JHJ (1993): The relationship between affinity progestins and anti-progestins for the progesterone receptor in breast cancer cells (ZR-PR-LT) and ability to down-regulate the receptor: Modulation via the glucocorticoid receptor. Eur J Cancer 29A:1771–1775.

    PubMed  Google Scholar 

  • Van der Schoot P, Bakker GH, Klijn JGM (1987): Effects of the progesterone antagonist RU 486 (Mifepristone) on ovarian activity in the rat. Endocrinol 121:1375–1382.

    Article  Google Scholar 

  • Vollmer G, Michna H, Ebert K, Knuppen R (1992): Down-regulation of tenascin expression by antiprogestins during terminal differentiation of rat mammary tumors. Cancer Res 52:4642–1648.

    PubMed  CAS  Google Scholar 

  • von Angerer E, Knebel N, Kager M, Ganss B (1990): 1-Aminoalkyl-2-phenylindoles as novel pure estrogen antagonists. J Med Chem 33:2653–2640.

    Google Scholar 

  • Wakeling AE, Dukes M, Bowler J (1991): A potent specific pure antiestrogen with clinical potential. Cancer Res 51:3867–3873.

    PubMed  CAS  Google Scholar 

  • Wakeling AE, Bowler J (1987): Steroidal pure antiestrogens. J Endocrinol 112:R7–10.

    Article  PubMed  CAS  Google Scholar 

  • Wakeling AE, Bowler J (1988): Biology and mode of action of pure antiestrogens. J Steroid Biochem 30:141–149.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Morphology and Tumor Research, DSHS, 50933, Cologne, Germany

    Horst Michna, Yukishige Nishino, Karsten Parczyk & Martin R. Schneider

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  1. Horst Michna
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  2. Yukishige Nishino
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  3. Karsten Parczyk
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  4. Martin R. Schneider
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Editors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Kentucky Medical Center, 800 Rose Street, 40536-0084, Lexington, KY, USA

    Edward J. Pavlik

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© 1997 Birkhäuser Boston

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Michna, H., Nishino, Y., Parczyk, K., Schneider, M.R. (1997). Antiprogestins: Past, Present, and Future. In: Pavlik, E.J. (eds) Estrogens, Progestins, and Their Antagonists. Hormones in Health and Disease. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4096-9_11

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  • DOI: https://doi.org/10.1007/978-1-4612-4096-9_11

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4612-8650-9

  • Online ISBN: 978-1-4612-4096-9

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