Contragestion and Other Clinical Applications of RU 486, an Antiprogesterone at the Receptor
SciencePublished 22 September 1989
Étienne-Émile Baulieu
Citations489
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
RU 486, a steroid with high affinity for the progesterone receptor, is the first available active antiprogesterone, and it has been used successfully as a medical alternative for early pregnancy interruption.
Abstract
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.
Keywords
Immunology and MicrobiologyMedicineBiochemistry, Genetics and Molecular Biology
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317 Citations1985Lynnette K. Nieman, George P. Chrousos +7 more
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The EMBO JournalSpecific glucocorticoid receptor binding to DNA reconstituted in a nucleosome.
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268 Citations1978Françis Bayard, S Damilano +2 more
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Journal of Biological ChemistryA region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.
268 Citations1988William B. Pratt, Dominique Jolly +8 more
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ContraceptionProgesterone receptor blockage
252 Citations1985M. Bygdeman, M.L. Swahn
Withdrawal of progesterone locally by RU 486 treatment resulted in the development of a regular uterine activity which was in sharp contrast to the low level contractility pattern found in the untreated control patients.
The Journal of Clinical Endocrinology & MetabolismThe New Steroid Analog RU 486 Inhibits Glucocorticoid Action in Man
237 Citations1984Xavier Bertagna, C. Bertagna +3 more
It is concluded that RU 486 antagonizes the negative pituitary feedback of both the nocturnal endogenous cortisol rise and exogenously administered dexamethasone, consistent with an antiglucocorticoid activity of this compound in man.
New England Journal of MedicineTermination of Early Pregnancy by the Progesterone Antagonist RU 486 (Mifepristone)
237 Citations1986Béatrice Couzinet, Nelly Le Strat +3 more
It is concluded that RU 486 is an effective and safe method for termination of very early pregnancy but that it should be used only under close medical supervision.
The Journal of Clinical Endocrinology & MetabolismInduction of Midcycle Gonadotropin Surge by Ovarian Steroids in Women: A Critical Evaluation*
224 Citations1983J. H. LlU, S. S. C. YEN
This data represent the first unequivocal demonstration that incremental E2 sustained for about 60 h constitutes the ovarian signal for initiating the midcycle gonadotropin surge and that a small increment of P4 secreted by the preovulatory follicle is required to establish the normal dimension of the surge.
Journal of Molecular BiologySteroid-induced nuclear binding of glucocorticoid receptors in intact hepatoma cells
220 Citations1973Guy Rousseau, John D. Baxter +2 more
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Proceedings of the National Academy of SciencesRU 486: a steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day.
216 Citations1984Rolf C. Gaillard, A. Riondel +3 more
The results indicate that RU 486 is an antiglucocorticosteroid that disrupts the negative pituitary feedback of both the morning cortisol rise and administered dexamethasone and demonstrate the possibility of optimizing the anti-progestational effect of the compound and its potential use for human fertility control by modifying the dose and the time of administration of the drug.
ContraceptionTermination of very early pregnancy by RU 486 — An antiprogestational compound
209 Citations1984László Kovács, M. Sas +5 more
It is concluded that treatment with RU 486 may provide a novel therapy for "menstrual regulation" but the efficacy of the treatment needs to be improved to compete with alternatives such as vacuum aspiration.
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191 Citations1988Lisa L. Wei, Nancy Krett +5 more
Analysis of RNA blot hybridization analysis of poly(A+) RNA shows that T47DCO, an estrogen resistant human breast tumor cell line in which PR are constitutively expressed, contain at least six PR mRNAs, suggesting that progestational agonists autoregulate the levels of their own receptors by inhibiting transcription of the PR gene.
The Journal of Clinical Endocrinology & MetabolismEndometrial and Pituitary Responses to the Steroidal Antiprogestin RU 486in Postmenopausal Women
190 Citations1985Achille Gravanis, G Schaison +5 more
It is concluded that, contrary to previous results with experimental animals, the anti-P RU 486 has some progestomimetic activity in humans under specific conditions.
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186 Citations1984John J. Dougherty, Raj K. Puri +1 more
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158 Citations1987J. H. LIU, Gabriel Garzo +4 more
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The EMBO JournalDNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU‐486.
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137 Citations1985G Schaison, Martine George +3 more
RU 486, given to normally cycling women at midluteal phase, provokes uterine bleeding and the lack of antiglucocorticosteroid activity, at the dosage of 100 mg/day, suggests that RU 486 may be useful for fertility control.
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130 Citations1985Kathryn B. Horwitz
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128 Citations1983Ingrid Jung‐Testas, Étienne-Émile Baulieu
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127 Citations1987Heikinheimo Oskari, Kontula Kimmo +4 more
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ContraceptionTherapeutic abortion in early pregnancy with antiprogestogen RU486 alone or in combination with prostaglandin analogue (Gemeprost)
118 Citations1986I.T. Cameron, Alison F. Michie +1 more
It is concluded that the combination of RU486 and a single PG vaginal pessary is a highly effective means of inducing therapeutic abortion in early pregnancy and offers an alternative to surgery.
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106 Citations1986W. Elger, S. Beier +6 more
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104 Citations1986Robert L. Collins, Gary D. Hodgen
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86 Citations1985David Healy, George P. Chrousos +3 more
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84 Citations1988V. Gabriel Garzo, J. LIU +3 more
The impact of the antiprogesterone RU486 on the hypothalamic-pituitary-ovarian-endometrial axis was examined in normal cycling women during the mid (MLP)- and late (LLP) luteal phases and showed significant decreases in LH secretion and LH pulse amplitude and blunted pituitary responses to GnRH.
American Journal of Obstetrics and GynecologyTemporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation
82 Citations1987George J. Haluska, Frank Z. Stanczyk +2 more
Control animals but not those given RU486 demonstrated a progressive nocturnal peak in uterine activity before delivery, which contrasts with the orderly sequence of changes in prostaglandins and cervical status observed during normal parturition.
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81 Citations1973Robert Schimke, Rafael Palacios +2 more
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74 Citations1988Angelique Flöter Rådestad, Niels Juel Christensen +1 more
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72 Citations1987Donna Shoupe, Daniel R. Mishell +5 more
There was a significant decline in follicle-stimulating hormone, estradiol, and progesterone over the 48-hour sampling period, but there was no change in these values in the group with two bleeding episodes.
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68 Citations1989Jean Philippe Wolf, Michael J. Sinosich +4 more
A progesterone antagonist (RU 486), combined with oxytocin, was effective in achieving cervical dilation, labor induction, and early delivery in near-term monkeys.
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68 Citations1988M.L. Swahn, E. Johannisson +3 more
The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle, and the length of the follow-up cycle was similar to that of the control cycle.
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68 Citations1985André Groyer, Yves Le Bouc +5 more
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66 Citations1989Nadine Binart, Béatrice Chambraud +7 more
The Journal of Clinical Endocrinology & MetabolismThe Effect of the Antiprogestins RU 486 and ZK 98734 on the Synthesis and Metabolism of Prostaglandins F<sub>2<i>α</i></sub>and E<sub>2</sub>in Separated Cells from Early Human Decidua
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66 Citations1986Marilyn J. Koering, David Healy +1 more
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European Journal of BiochemistryMechanism of action of an antiprogesterone, RU486, in the rabbit endometrium
65 Citations1985Michel Rauch, Hugues Loosfelt +2 more
The induction of uteroglobin mRNA by progesterone in the rabbit endometrium may be a suitable model for studies since RU486 totally inhibits this effect without itself exerting any agonistic activity, and the fact that this compound is a complete antagonist without any agonists activity can only be explained by a defect in some further step of hormone action.
Journal of Steroid Biochemistry11β-substituted steroids, an original pathway to antihormones
63 Citations1988Georges Teutsch, Tiiu Ojasoo +1 more
The comparison of the 3D-structures of these antagonists with those of potent hormones can help to map the interaction sites with PR and GR and highlights the potential use of these molecules as labelling agents and molecular probes.
Fertility and SterilityThe effects of progesterone receptor blockade in the luteal phase of normal fertile women
59 Citations1988Tin Chiu Li, Peter Dockery +4 more
Both menstrual induction and changes in hypothalamic function after the administration of RU486 occurred independently of luteolysis and so were likely to be the direct result of progesterone receptor blockade in these organs.
Fertility and SterilityContragestion with late luteal administration of RU 486 (Mifepristone)
59 Citations1988Catherine Dubois, André Ulmann +1 more
This method is acceptable for women at risk of pregnancy in whom other usual postcoital contraceptive methods cannot be prescribed, and there was no disturbance in the menstrual cycle, and the tolerance was very satisfactory.
BiochemistryTransformation of calf uterine progesterone receptor: analysis of the process when receptor is bound to progesterone and RU38486
52 Citations1987V.K. Moudgil, Cliff Hurd
An aqueous two-phase partitioning analysis revealed a significant change in the surface properties of PR following both binding to ligand and subsequent transformation, which increased about 5-fold over that observed with PR at 0 degrees C.
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52 Citations1979Nadine Binart, M.G. Catelli +5 more
It is concluded that antioestrogenic action may be exhibited by a molecule with higher affinity binding to the oestrogen receptor than oestradiol itself, and not due to its prior conversion to monohydroxytamoxifen.
ContraceptionContraceptive potential of RU 486 by ovulation inhibition: I. Pituitary versus ovarian action with blockade of estrogen induced endometrial proliferation
50 Citations1989Jan F.H.M. van Uem, Jeng G. Hsiu +5 more
Findings show that RU 486 prevented ovulation by diminishing pituitary gonadotropin secretion, rather than by direct effects on ovarian folliculogenesis, and induced amenorrhea by inhibiting estrogen-induced endometrial proliferation.
Journal of Steroid BiochemistryGlucocorticoid receptors bound to the antagonist RU486 are not downregulated despite their capacity to interact in vitro with defined gene regions
48 Citations1987Ewa J. Rajpert, Frédéric P. Lemaigre +7 more
Although cell-free receptor dissociation and therefore DNA binding can occur even when the receptor is bound to RU486, this steroid maintains receptors in the untransformed state in the intact cell and therefore behaves a glucocorticoid antagonist in vivo.
TetrahedronScript: interactive molecular geometrical treatments on the basis of computer-drawn chemical formula
47 Citations1981N.C. Cohen, P. Colin +1 more
SCRIPT is a conversational computer program which reveals the conformers and their relative energies for a given organic compound and shows that bulky substituents at 17α lead to a more stable quasi-cis C/D conformation which cannot be constructed with standard Dreiding models.
BiochemistryCovalent stabilization of the nontransformed chick oviduct cytosol progesterone receptor by chemical crosslinking
46 Citations1988Péter Arányi, Christine Radanyi +3 more
It was found that the dimethyl pimelimidate cross-linked 8S-PR was more resistant to inactivating conditions, urea, or heat treatment than the non-cross-linked 4-S sedimentation coefficient.
Fertility and SterilityMedical treatment of residual ectopic pregnancy: RU 486 and methotrexate
46 Citations1987Daniel Kenigsberg, Jeffrey Porte +2 more
American Journal of Obstetrics and GynecologyEarly abortion with a single dose of the antiprogestin RU-486
45 Citations1988David A. Grimes, Daniel R. Mishell +2 more
Uterine bleeding was the most serious side effect, however, the mean change in the hemoglobin value 14 days after treatment was -0.4 gm/dl, and no patient required blood transfusion, and this regimen appears to be simple, effective, and safe.
Human ReproductionEfficacy of progesterone antagonist RU486 (Mifepristone) for pre-operative cervical dilatation during first trimester abortion
44 Citations1988Florence Durlot, Cathérine Dubois +2 more
It is concluded that the consistency of the cervix changed significantly after RU486, and this effect may facilitate cervical dilatation, making first trimester abortion under local anaesthesia more comfortable and less dangerous.
Journal of Steroid BiochemistryScreening of anti-progestagens by receptor studies and bioassays
44 Citations1988H.J. Kloosterboer, G.H. Deckers +2 more
Two compounds tested with the dimethylaminophenyl group at carbon atom 18 of 17 beta-hydroxy-17 alpha-(2-propenyl)-estra-4-en-3-one are equipotent with RU 38486 in the pregnancy interruption test, and it is very likely that they become activated in the gastro-intestinal tract.
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44 Citations1988Dorraya El-Ashry-Stowers, David T. Zava +2 more
Data from monoclonal antibodies used for immunocytochemical localization of PR are consistent with progestins down regulating their own receptors due to a loss in cellular PR content and not to inactivation of receptors.
ContraceptionTermination of early gestation with the anti-progestin steroid RU 486: Medium versus low dose
44 Citations1987Daniel R. Mishell, Donna Shoupe +5 more
RU 486 is a promising agent for termination of early pregnancy and has shown promise in women with normal pregnancies whose gestational duration was less than 49 days from onset of last menses.
Experimental Biology and MedicineInduction of Avidin Formation in the Avian Oviduct by Stilbestrol Plus Progesterone
44 Citations1943R. Hertz, R. M. Fraps +1 more
This finding demonstrates a specific effect of progesterone in the bird, and suggests that the avidin-biotin complex may play a role in the physiology of avian reproduction.
Fertility and SterilityCompetitive Progesterone Antagonists: Receptor Binding and Biologic Activity of Testosterone and 19-Nortestosterone Derivatives
41 Citations1979Jerry R. Reel, Ronald R. Humphrey +5 more
Results demonstrate that several 19-nortestosterone derivatives bind to the uterine progesterone receptor and behave either as antagonists or mixed agonists/antagonists.
The LancetANTIFERTILITY ACTIONS OF THE PROGESTERONE ANTAGONIST RU 486 INCLUDE DIRECT INHIBITION OF PLACENTAL HORMONE SECRETION
41 Citations1987Chandra Das, K. J. Catt
The specific inhibitory effects of RU 486 on placental hormone secretion indicate that its antifertility actions are attributable to competitive inhibition of progesterone action in the trophoblast as well as in the endometrium.
Fertility and SterilityLate postcoital treatment against pregnancy with antiprogesterone RU 486
40 Citations1988Pekka Lähteenmäki, Timo Rapeli +3 more
BiochemistryAssociation of the glucocorticoid receptor binding subunit with the 90K nonsteroid-binding component is stabilized by both steroidal and nonsteroidal antiglucocorticoids in intact cells
39 Citations1988Philippe Lefèbvre, Pierre Marie Danzé +4 more
The data, demonstrating for the first time that all antiglucocorticoids probably act via a common mechanism, suggest a key role for subunit dissociation during in vivo receptor activation.
Fertility and SterilityEarly pregnancy termination with antiprogestins: a comparative clinical study of RU 486 given in two dose regimens and Epostane
39 Citations1987Lars Birgerson, Viveca Odlind
Journal of Steroid BiochemistryThe mechanism of action of steroid antagonists: Insights from crystallographic studies
37 Citations1988William L. Duax, Jane F. Griffin +2 more
With the exception of the androgens, the data suggest that specific interactions between the steroid B-, C- and D-rings and the receptor play at best a minor role in receptor binding but are the most important factor in determining agonist versus antagonist behavior subsequent to binding.
Journal of Steroid BiochemistryRU486 is not an antiprogestin in the hamster
37 Citations1987Gary O. Gray, Wendell W. Leavitt
Molecular PharmacologyX-ray Crystallography of Estrogens and Their Binding to Receptor Sites
36 Citations1972M. Hospital, B. Busetta +2 more
It is proposed that the solvated asymmetrical form of diethylstilbestrol resembles more closely its "active" conformation when present in receptor binding sites, compatible with the estrogenic activity and binding affinity of the estradiol derivatives.
Human ReproductionMifepristone (RU486) and therapeutic late pregnancy termination: a double-blind study of two different doses
35 Citations1988René Frydman, Hervé Fernandez +2 more
An antiprogesterone, mifepristone (RU486), was administered to 35 patients undergoing a therapeutic interruption of pregnancy during the second and third trimester for maternal or fetal indications and produced a modification in the consistency of the cervix with a statistical improvement in cervical calibration in the two groups, but the cervical effect was independent of the dose.
Fertility and SterilityPharmacodynamics of the antiprogesterone RU486 in women after oral administration
33 Citations1988James Liu, Vincent Gabriel Garzo +1 more
It is suggested that the pharmacologic action of RU486 is prolonged after a single oral dose, because of the relatively slow clearance rate for RU486 and its metabolites.
Trends in Pharmacological SciencesThe use of interaction kinetics to distinguish potential antagonists from agonists
32 Citations1980Jean Raynaud
The kinetics of the interaction between a ligand and the cytosolic steroid hormone receptor is an important factor in determining the nature and amplitude of the induced biochemical and biological responses and can be used as the basis of a screening system to distinguish potential antagonists from potent agonists for every class of steroid hormone.
Biochemical and Biophysical Research CommunicationsAntiprogestin-receptor complexes: Differences in the interaction of the antiprogestin RU38,486 and the progestin R5020 with the progesterone receptor of human breast cancer cells
31 Citations1986Alaka Mullick, Benita S. Katzenellenbogen
Findings suggest that the 6 S antiprogestin complex is formed as a result of the interaction of PR units with each other or with a different protein, suggesting that disulfide bonds and hydrophobic interactions are important in maintaining the integrity of the 6S form.
European Journal of Obstetrics & Gynecology and Reproductive BiologyTermination of early pregnancy by a single dose of mifepristone (RU 486), a progesterone antagonist
30 Citations1988Bernard L. Maria, F Stampf +2 more
Mifepristone is able to terminate early pregnancy by an easy ambulatory method under medical supervision using a single oral dose of 600 mg, with a very few side-effects.
The Journal of Clinical Endocrinology & MetabolismLate Luteal Phase Administration of RU486 for Three Successive Cycles Does Not Disrupt Bleeding Patterns or Ovulation*
29 Citations1987Horacio B. Croxatto, Ana María Salvatierra +2 more
It is concluded that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.
Trends in Pharmacological SciencesDo antiestrogens and antiprogestins act as hormone antagonists or receptor-targeted drugs in breast cancer?
29 Citations1987Henri Rochefort
Henri Rochefort proposes that sex steroid antagonists inhibit breast cancer growth not only through their antihormonal activity, but also more directly as antimitogenic drugs targeted to nuclei via specific hormone receptors.
New England Journal of MedicineTermination of Early Pregnancy by the 3β-Hydroxysteroid Dehydrogenase Inhibitor Epostane
26 Citations1988M. J. CROOIJ, C. C. A. De Nooyer +4 more
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