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Science 22 September 1989:
Vol. 245. no. 4924, pp. 1351 - 1357
DOI: 10.1126/science.2781282

Articles

Science, Vol 245, Issue 4924, 1351-1357
Copyright © 1989 by American Association for the Advancement of Science


articles

Contragestion and other clinical applications of RU 486, an antiprogesterone at the receptor

EE Baulieu

INSERM U 33 (Communications hormonales), Faculte de Medicine, Universite Paris-Sud, Bicetre, France.

RU 486, a steroid with high affinity for the progesterone receptor, is the first available active antiprogesterone. It has been used successfully as a medical alternative for early pregnancy interruption, and it also has other potential applications in medicine and for biochemical and pathophysiological endocrine research.


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Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks.
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Progesterone Receptor B Recruits a Repressor Complex to a Half-PRE Site of the Estrogen Receptor {alpha} Gene Promoter.
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Progesterone and interferon tau regulate leukemia inhibitory factor receptor and IL6ST in the ovine uterus during early pregnancy.
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Progesterone Regulates FGF10, MET, IGFBP1, and IGFBP3 in the Endometrium of the Ovine Uterus.
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A Structural and in Vitro Characterization of Asoprisnil: A Selective Progesterone Receptor Modulator.
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Neuroprotective effect of mifepristone involves neuron depolarization.
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Toxicol. Sci. 90, 362-368
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Endocrine Regulation of Menstruation.
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The Unusual Binding Properties of the Third Distinct Teleost Estrogen Receptor Subtype ER{beta}a Are Accompanied by Highly Conserved Amino Acid Changes in the Ligand Binding Domain.
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Nongenomic Inhibition of Oxytocin Binding by Progesterone in the Ovine Uterus.
K. A. Dunlap and F. Stormshak (2004)
Biol Reprod 70, 65-69
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Immune-Responsive Gene 1 Is a Novel Target of Progesterone Receptor and Plays a Critical Role during Implantation in the Mouse.
Y.-P. Cheon, X. Xu, M. K. Bagchi, and I. C. Bagchi (2003)
Endocrinology 144, 5623-5630
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Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum.
A. M. Ghoumari, I. Dusart, M. El-Etr, F. Tronche, C. Sotelo, M. Schumacher, and E.-E. Baulieu (2003)
PNAS 100, 7953-7958
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The FK506-Binding Immunophilin FKBP51 Is Transcriptionally Regulated by Progestin and Attenuates Progestin Responsiveness.
T. R. Hubler, W. B. Denny, D. L. Valentine, J. Cheung-Flynn, D. F. Smith, and J. G. Scammell (2003)
Endocrinology 144, 2380-2387
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The Glucocorticoid Receptor as a Potential Target to Reduce Cocaine Abuse.
V. Deroche-Gamonet, I. Sillaber, B. Aouizerate, R. Izawa, M. Jaber, S. Ghozland, C. Kellendonk, M. Le Moal, R. Spanagel, G. Schutz, et al. (2003)
J. Neurosci. 23, 4785-4790
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Regulated Expression of Osteopontin in the Peri-Implantation Rabbit Uterus.
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Biol Reprod 68, 1484-1490
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Modulation of Induction Properties of Glucocorticoid Receptor-Agonist and -Antagonist Complexes by Coactivators Involves Binding to Receptors but Is Independent of Ability of Coactivators to Augment Transactivation.
Y. He, D. Szapary, and S. S. Simons Jr. (2002)
J. Biol. Chem. 277, 49256-49266
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Mechanism of Action of Progesterone Antagonists.
S. A. Leonhardt and D. P. Edwards (2002)
Experimental Biology and Medicine 227, 969-980
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A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation.
Y.-P. Cheon, Q. Li, X. Xu, F. J. DeMayo, I. C. Bagchi, and M. K. Bagchi (2002)
Mol. Endocrinol. 16, 2853-2871
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Identification and Characterization of Novel Estrogen Receptor-{beta}-Sparing Antiprogestins.
G. Sathya, M. S. Jansen, S. C. Nagel, C. E. Cook, and D. P. MCDonnell (2002)
Endocrinology 143, 3071-3082
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Signal Transducer and Activator of Transcription 3 Is Expressed in the Decidualized Mesometrium of Pregnancy and Associates with the Progesterone Receptor Through Protein-Protein Interactions.
T. Liu and T. F. Ogle (2002)
Biol Reprod 67, 114-118
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Structure/Activity Elements of the Multifunctional Protein, GMEB-1. CHARACTERIZATION OF DOMAINS RELEVANT FOR THE MODULATION OF GLUCOCORTICOID RECEPTOR TRANSACTIVATION PROPERTIES.
J. Chen, S. Kaul, and S. S. Simons Jr. (2002)
J. Biol. Chem. 277, 22053-22062
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Ubc9 Is a Novel Modulator of the Induction Properties of Glucocorticoid Receptors.
S. Kaul, J. A. Blackford Jr., S. Cho, and S. S. Simons Jr. (2002)
J. Biol. Chem. 277, 12541-12549
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Elevated Endometrial Androgen Receptor Expression in Women with Polycystic Ovarian Syndrome.
K.B.C. Apparao, L. P. Lovely, Y. Gui, R. A. Lininger, and B. A. Lessey (2002)
Biol Reprod 66, 297-304
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Characterization of 5'-regulatory region of human myostatin gene: regulation by dexamethasone in vitro.
K. Ma, C. Mallidis, J. Artaza, W. Taylor, N. Gonzalez-Cadavid, and S. Bhasin (2001)
Am J Physiol Endocrinol Metab 281, E1128-E1136
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Osteopontin and Its Receptor {alpha}v{beta}3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially.
K. B. C. Apparao, M. J. Murray, M. A. Fritz, W. R. Meyer, A. F. Chambers, P. R. Truong, and B. A. Lessey (2001)
J. Clin. Endocrinol. Metab. 86, 4991-5000
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Mifepristone (RU486) and voluntary termination of pregnancy: enigmatic variations or anecdotal religion-based attitudes?.
E.-E. Baulieu, D. S. Seidman, and S. Hajri (2001)
Hum. Reprod. 16, 2243-2244
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Perspective: Reproductive Endocrinology and Human Health in the 20th Century--A Personal Retrospective.
N. B. Schwartz (2001)
Endocrinology 142, 2163-2166
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New Antiprogestins with Partial Agonist Activity: Potential Selective Progesterone Receptor Modulators (SPRMs) and Probes for Receptor- and Coregulator-Induced Changes in Progesterone Receptor Induction Properties.
G. Giannoukos, D. Szapary, C. L. Smith, J. E. W. Meeker, and S. S. Simons Jr. (2001)
Mol. Endocrinol. 15, 255-270
   Abstract »    Full Text »
Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets.
G. Wu, N. E. Flynn, and D. A. Knabe (2000)
Am J Physiol Endocrinol Metab 279, E395-E402
   Abstract »    Full Text »    PDF »
A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning.
G. Wu, N. E. Flynn, D. A. Knabe, and L. A. Jaeger (2000)
Am J Physiol Regulatory Integrative Comp Physiol 279, R554-R559
   Abstract »    Full Text »    PDF »
Regression of the Decidualized Mesometrium and Decidual Cell Apoptosis Are Associated with a Shift in Expression of Bcl2 Family Members.
D. Dai, B. C. Moulton, and T. F. Ogle (2000)
Biol Reprod 63, 188-195
   Abstract »    Full Text »
Medical Termination of Pregnancy.
S. Christin-Maitre, P. Bouchard, and I. M. Spitz (2000)
N. Engl. J. Med. 342, 946-956
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E1A-Mediated Repression of Progesterone Receptor-Dependent Transactivation Involves Inhibition of the Assembly of a Multisubunit Coactivation Complex.
Y. Xu, L. Klein-Hitpass, and M. K. Bagchi (2000)
Mol. Cell. Biol. 20, 2138-2146
   Abstract »    Full Text »
Cloning and Uterus/Oviduct-specific Expression of a Novel Estrogen-regulated Gene (ERG1).
D. Chen, X. Xu, L.-J. Zhu, M. Angervo, Q. Li, M. K. Bagchi, and I. C. Bagchi (1999)
J. Biol. Chem. 274, 32215-32224
   Abstract »    Full Text »    PDF »
Effect of adrenocorticotrophic hormone on sodium appetite in mice.
D. A. Denton, J. R. Blair-West, M. I. McBurnie, J. A. P. Miller, R. S. Weisinger, and R. M. Williams (1999)
Am J Physiol Regulatory Integrative Comp Physiol 277, R1033-R1040
   Abstract »    Full Text »    PDF »
Progesterone Regulation of Epidermal Growth Factor Receptor in Rat Decidua Basalis during Pregnancy.
D. Dai and T. F. Ogle (1999)
Biol Reprod 61, 326-332
   Abstract »    Full Text »
Glucocorticoids Mediate the Enhanced Expression of Intestinal Type II Arginase and Argininosuccinate Lyase in Postweaning Pigs.
N. E. Flynn, C. J. Meininger, K. Kelly, N. H. Ing, S. M. Morris Jr., and G. Wu (1999)
J. Nutr. 129, 799-803
   Abstract »    Full Text »
The Novel Progesterone Receptor Antagonists RTI 3021-012 and RTI 3021-022 Exhibit Complex Glucocorticoid Receptor Antagonist Activities: Implications for the Development of Dissociated Antiprogestins.
B. L. Wagner, G. Pollio, P. Giangrande, J. C. Webster, M. Breslin, D. E. Mais, C. E. Cook, W. V. Vedeckis, J. A. Cidlowski, and D. P. McDonnell (1999)
Endocrinology 140, 1449-1458
   Abstract »    Full Text »
Progesterone Induces Calcitonin Gene Expression in Human Endometrium within the Putative Window of Implantation.
S. Kumar, L.-J. Zhu, M. Polihronis, S. T. Cameron, D. T. Baird, F. Schatz, A. Dua, Y.-K. Ying, M. K. Bagchi, and I. C. Bagchi (1998)
J. Clin. Endocrinol. Metab. 83, 4443-4450
   Abstract »    Full Text »
Calcitonin Is a Progesterone-Regulated Marker That Forecasts the Receptive State of Endometrium during Implantation.
L.-J. Zhu, K. Cullinan-Bove, M. Polihronis, M. K. Bagchi, and I. C. Bagchi (1998)
Endocrinology 139, 3923-3934
   Abstract »    Full Text »    PDF »
A Nuclear Receptor Corepressor Modulates Transcriptional Activity of Antagonist-Occupied Steroid Hormone Receptor.
X. Zhang, M. Jeyakumar, S. Petukhov, and M. K. Bagchi (1998)
Mol. Endocrinol. 12, 513-524
   Abstract »    Full Text »
The Antagonists RU486 and ZK98299 Stimulate Progesterone Receptor Binding to Deoxyribonucleic Acid in Vitro and in Vivo, but Have Distinct Effects on Receptor Conformation.
E. K. Gass, S. A. Leonhardt, S. K. Nordeen, and D. P. Edwards (1998)
Endocrinology 139, 1905-1919
   Abstract »    Full Text »    PDF »
Synthetic Glucocorticoids That Dissociate Transactivation and AP-1 Transrepression Exhibit Antiinflammatory Activity in Vivo.
B. M. Vayssière, S. Dupont, A. Choquart, F. Petit, T. Garcia, C. Marchandeau, H. Gronemeyer, and M. Resche-Rigon (1997)
Mol. Endocrinol. 11, 1245-1255
   Abstract »    Full Text »
Antiprogestin Inhibition of Cell Cycle Progression in T-47D Breast Cancer Cells Is Accompanied by Induction of the Cyclin-Dependent Kinase Inhibitor p21.
E. A. Musgrove, C. S. L. Lee, A. L. Cornish, A. Swarbrick, and R. L. Sutherland (1997)
Mol. Endocrinol. 11, 54-66
   Abstract »    Full Text »
Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities..
J P Lydon, F J DeMayo, C R Funk, S K Mani, A R Hughes, C A Montgomery, G Shyamala, O M Conneely, and B W O'Malley (1995)
Genes & Dev. 9, 2266-2278
   Abstract »    PDF »
Mifepristone (RU 486) -- A Modulator of Progestin and Glucocorticoid Action.
I. M. Spitz and C.W. Bardin (1993)
N. Engl. J. Med. 329, 404-412
   Full Text »
Mifepristone (RU 486) in the United States -- What Does the Future Hold?.
A. Rosenfield (1993)
N. Engl. J. Med. 328, 1560-1561
   Full Text »
Structural reorganization of the rough endoplasmic reticulum without size expansion accounts for dexamethasone-induced secretory activity in AR42J cells.
A. Rajasekaran, T Morimoto, D. Hanzel, E Rodriguez-Boulan, and G Kreibich (1993)
J. Cell Sci. 105, 333-345
   Abstract »    PDF »
RU 486: The Progesterone Antagonist.
B. D. Weiss (1993)
Arch Fam Med 2, 63-69
   Abstract »    PDF »
Updating RU 486 Development.
E.-E. Baulieu (1992)
J. Law Med. Ethics 20, 154-156
   PDF »
Mifepristone Blocks Specific Glucocorticoid Receptor Binding in Rabbit Iris--Ciliary Body.
P. M. Munden and T. J. Schmidt (1992)
Arch Ophthalmol 110, 703-705
   Abstract »    PDF »
A single amino acid that determines the sensitivity of progesterone receptors to RU486.
B Benhamou, T Garcia, T Lerouge, A Vergezac, D Gofflo, C Bigogne, P Chambon, and H Gronemeyer (1992)
Science 255, 206-209
   Abstract »    PDF »
Response: Steroid Binding at sgr-"Opioid" Receptors.
T.-P. SU, E. D. LONDON, and J. H. JAFFE (1989)
Science 246, 1637-1638
   PDF »
RU 486: THE ""ABORTION PILL"".
(1989)
Journal Watch (General) 1989, 3
   Full Text »



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