Mechanisms controlling agonist and antagonist potential of selective progesterone receptor modulators (SPRMs)

Seminars in Reproductive Medicine

Volumn 23, Issue 1, 2005, Pages 9-21

  Wardell, Susanne E ^b   Edwards, Dean P ^a,b  

^a University of Colorado Anschutz Medical Campus   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

N domain AF 1; Progesterone antagonists; Progesterone receptor; RU 486 (mifepristone); Selective progesterone receptor modulators

Indexed keywords

ANTIESTROGEN; ANTIGESTAGEN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; ESTROGEN; ESTROGEN RECEPTOR ALPHA; LEUCINE ZIPPER PROTEIN; MIFEPRISTONE; NUCLEAR RECEPTOR COREPRESSOR; ONAPRISTONE; PROGESTERONE RECEPTOR; PROGESTERONE RECEPTOR MODULATOR; RNA POLYMERASE II; STEROID RECEPTOR; TAMOXIFEN; TRANSCRIPTION FACTOR;

AGONIST; AMINO TERMINAL SEQUENCE; BREAST EPITHELIUM; CARBOXY TERMINAL SEQUENCE; CELL PROLIFERATION; CONTROL SYSTEM; DNA BINDING; DRUG ANTAGONISM; HUMAN; LIGAND BINDING; MITOGENESIS; PROTEIN CONFORMATION; PROTEIN INTERACTION; REVIEW; TRANSACTIVATION; UTERUS;

HORMONE ANTAGONISTS; HUMANS; MIFEPRISTONE; PROGESTERONE; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, PROGESTERONE; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION, GENETIC;

EID: 14744300083     PISSN: 15268004     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2005-864030     Document Type: Review

References (120)

1. Conneely O, Jericevic B, Lydon J. Progesterone receptors in mammary gland development and tumorigenesis. J Mammary Gland Biol Neoplasia 2003;8:205-214
2. Conneely O, Mulac-Jericevic B, DeMayo F, Lydon J, O'Malley B. Reproductive functions of progesterone receptors. Recent Prog Horm Res 2002;57:339-355
3. Moutsatsou P, Sekeris C. Steroid receptors in the uterus: implications in endometriosis. Ann N Y Acad Sci 2003;997:209-222
4. Neville M. Physiology of lactation. Clin Perinatol 1999;26:251-279
5. Yasui T, Uemura H, Takikawa M, Irahara M. Hormone replacement therapy in postmenopausal women. J Med Invest 2003;50:136-145
6. Turgeon J, McDonnell D, Martin K, Wise P. Hormone therapy: physiological complexity belies therapeutic simplicity. Science 2004;304:1269-1273
7. Samsioe G. HRT and cardiovascular disease. Ann N Y Acad Sci 2003;997:358-372
8. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000;283:485-491
9. Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C. Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Cancer Causes Control 1999;10:253-260
10. Spitz I, Croxatto H, Robbins A. Antiprogestins: mechanism of action and contraceptive potential. Annu Rev Pharmacol Toxicol 1996;36:47-81
11. Horwitz K. The molecular biology of RU486. Is there a role of antiprogestins in the treatment of breast cancer? Endocr Rev 1992;13:146-163
12. Li X, O'Malley B. Unfolding the action of progesterone receptors. J Biol Chem 2003;278:39261-39264
13. Petz L, Nardulli A, Kim J, Horwitz K, Freedman L, Shapiro D. DNA bending is induced by binding of the glucocorticoid receptor DNA binding domain and progesterone receptors to their response elements. J Steroid Biochem Mol Biol 1997;60:31-41
14. Prendergast P, Pan Z, Edwards D. Progesterone receptor-induced bending of its target DNA: distinct effects of the A and B receptor forms. Mol Endocrinol 1996;10:393-407
15. Wen D, Xu Y-F, Mais D, Goldman M, McDonnell D. The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells. Mol Cell Biol 1994;14:8356-8364
16. Hovland A, Powell R, Takimoto G, Horwitz K. An N-terminal inhibitory function, IF, suppresses transcription by the A-isoform but not the B-isoform of human progesterone receptors. J Biol Chem 1998;273:5455-5460
17. Giangrande P, Pollio G, McDonnell D. Mapping and characterization of the functional domains responsible for the differential activity of the A and B isoforms of the human progesterone receptor. J Biol Chem 1997;272:32889-32900
18. Giangrande P, Kimbrel E, Edwards D, McDonnell D. The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding. Mol Cell Biol 2000;20:3102-3115
19. Bourguet W, Germain P, Gronemeyer H. Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol Sci 2000;21:381-387
20. Steinmetz A, Renaud J-P, Moras D. Binding of ligands and activation of transcription by nuclear receptors. Annu Rev Biophys Biomol Struct 2001;30:329-359
21. Egner U, Heinrich N, Ruff M, Gangloff M, Mueller-Fahrnow A, Wurtz J-M. Different ligands-different receptor conformations: modeling of the hERα LBD in complex with agonists and antagonists. Med Res Rev 2001;21:523-539
22. Weatherman R, Fletterick R, Scanlan T. Nuclear-receptor ligands and ligand-binding domains. Annu Rev Biochem 1999;68:559-581
23. McKenna N, Lanz R, O'Malley B. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999;20:321-344
24. Edwards D. The role of coactivators and corepressors in the biology and mechanism of action of steroid hormone receptors. J Mammary Gland Biol Neoplasia 2000;5:295-310
25. Glass C, Rosenfeld M. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000;14:121-141
26. Feng W, Ribeiro R, Wagner R, et al. Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors. Science 1998;280:1747-1749
27. Heery D, Kalkhoven E, Hoare S, Parker M. A signature motif in transcriptional coactivators mediates binding to nuclear receptors. Nature 1997;387:733-736
28. Leo C, Chen J. The SRC family of nuclear receptor coactivators. Gene 2000;245:1-11
29. Hong H, Kohli K, Garabedian M, Stallcup M. GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. MolCell Biol 1997;17:2735-2744
30. Yao T-P, Ku G, Zhou N, Scully R, Livingston D. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc Natl Acad Sci USA 1996;93:10626-10631
31. Spencer T, Jenster G, Burcin M, et al. Steroid receptor coactivator-1 is a histone acetyltransferase. Nature 1997;389:194-198
32. Kurokawa R, Kalafus D, Ogliastro M-H, et al. Differential use of CREB binding protein-coactivator complexes. Science 1998;279:700-703
33. Koh S, Chen D, Lee Y-H, Stallcup M. Synergistic enhancement of nuclear receptor function by p160 coactivators and two coactivators with protein methyltransferase activities. J Biol Chem 2001;276:1089-1098
34. Chen D, Ma H, Hong H, et al. Regulation of transcription by a protein methyltransferase. Science 1999;284:2174-2177
35. Ogryzko V, Schiltz R, Russanova V, Howard B, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 1996;87:953-959
36. Schwabe J, Neuhaus D, Rhodes D. Solution structure of the DNA binding domain of the oestrogen receptor. Nature 1990;348:458-461
37. Hard T, Kellenbach E, Boelens R, et al. Solution structure of the glucocorticoid receptor DNA binding domain. Science 1990;249:157-160
38. van Tilborg M, Lefstin J, Kruiskamp M, et al. Mutations in the glucocorticoid receptor DNA-binding domain mimic an allosteric effect in DNA. J Mol Biol 2000;301:947-958
39. Lefstin J, Thomas J, Yamamoto K. Influence of a steroid receptor DNA-binding domain on transcriptional regulatory functions. Genes Dev 1994;8:2842-2856
40. Godowski P, Picard D, Yamamoto K. Signal transduction and transcriptional regulation by glucocorticoid receptor-LexA fusion proteins. Science 1988;241:812-816
41. Lefstin J, Yamamoto K. Allosteric effects of DNA on transcriptional regulators. Nature 1998;392:885-888
42. Loven M, Wood J, Nardulli A. Interaction of estrogen receptors α and β with estrogen response elements. Mol Cell Endocrinol 2001;181:151-163
43. Wood J, Greene G, Nardulli A. Estrogen response elements function as allosteric modulators of receptor conformation. Mol Cell Biol 1998;18:1927-1934
44. Wood J, Likhite V, Loven M, Nardulli A. Allosteric modulation of estrogen receptor conformation by different estrogen response elements. Mol Endocrinol 2001;15:1114-1126
45. Hall J, McDonnell D, Korach K. Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements. Mol Endocrinol 2002;16:469-486
46. Blanco J, Minucci S, Lu J, et al. The histone acetylase PCAF is a nuclear receptor coactivator. Genes Dev 1998;12:1638-1651
47. Wardell S, Boonyaratanakornkit V, Adelman J, Aronheim A, Edwards D. Jun dimerization protein 2 functions as a progesterone receptor N-terminal domain coactivator. Mol Cell Biol 2002;22:5451-5466
48. Ko L, Cardona G, Henrion-Caude A, Chin W. Identification and characterization of a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors. Mol Cell Biol 2002;22:357-369
49. Allan G, Leng S, Tsai S, et al. Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation. J Biol Chem 1992;267:19513-19520
50. Vegeto E, Allan G, Schrader W, Tsai M-J, McDonnell D, O'Malley B. The mechanism of RU486 antagonism in dependent on the conformation of the carboxyl-terminal tail of the human progesterone receptor. Cell 1992;69:703-713
51. Brzozowski A, Pike A, Dauter Z, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997;389:753-757
52. Shiau A, Barstad D, Loria P, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonistm of this interaction by tamoxifen. Cell 1998;95:927-937
53. Wagner B, Norris J, Knotts T, Weigel N, McDonnell D. 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. Mol Cell Biol 1998;18:1369-1378
54. Jackson T, Richer J, Bain D, Takimoto G, Tung L, Horwitz K. The partial agonist activity of antagonist-occupied steroid receptors is controlled by a novel hinge domain-binding coactivator L7/SPA and the corepressors N-CoR and SMRT. Mol Endocrinol 1997;11:693-705
55. Smith C, Nawaz Z, O'Malley B. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol 1997;11:657-666
56. Zhang X, Jeyakumar M, Petukhov S, Bagchi M. A nuclear receptor corepressor modulates transcriptional activity of antagonist-occupied steroid hormone receptor. Mol Endocrinol 1998;12:513-524
57. Zamir I, Zhang J, Lazar M. Stoichiometric and steric principles governing repression by nuclear hormone receptors. Genes Dev 1997;11:835-846
58. Hu X, Lazar M. The CoRNR motif controls the recruitment of corepressors by nuclear hormone repressors. Nature 1999;402:93-96
59. Nagy L, Kao H-Y, Love J, et al. Mechanism of corepressor binding and release from nuclear hormone receptors. Genes Dev 1999;13:3209-3216
60. Perissi V, Staszewski L, McInerney E, et al. Molecular determinants of nuclear receptor-corepressor interaction. Genes Dev 1999;13:3198-3208
61. Wagner B, Pollio G, Leonhardt S, et al. 16a-substituted analogs of the antiprogestin RU486 induce a unique conformation in the human progesterone receptor resulting in mixed agonist activity. Proc Natl Acad Sci USA 1996;93:8739-8744
62. Meyer M-E, Pornon A, Ji J, Bocquel M-T, Chambon P, Gronemeyer H. Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor. EMBO J 1990;9:3923-3932
63. Klein-Hitpass L, Cato A, Henderson D, Ryffel G. Two types of antiprogestins indentified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acids Res 1991;19:1227-1234
64. Gass E, Leonhardt S, Nordeen S, Edwards D. The antagonists RU486 and ZK98299 stimulate progesterone receptor binding to deoxyribonucleic acid in vitro and in vivo, but have distinct effects on receptor conformation. Endocrinology 1998;139:1905-1919
65. Tetel M, Giangrande P, Leonhardt S, McDonnell D, Edwards D. Hormone-dependent interaction between the amino- and carboxyl-terminal domains of progesterone receptor in vitro and in vivo. Mol Endocrinol 1999;13:910-924
66. Leonhardt S, Edwards D. Mechanism of action of progesterone antagonists. Exp Biol Med 2002;227:969-980
67. Leonhardt S, Altmann M, Edwards D. Agonist and antagonists induce homodimerization and mixed ligand heterodimerization of human progesterone receptors in vivo by mammalian two-hybrid assay. Mol Endocrinol 1998;12:1914-1930
68. El-ashry D, Onãte S, Nordeen S, Edwards D. Human progesterone receptor complexed with the antagonist RU486 binds to hormone response elements in a structurally altered form. Mol Endocrinol 1989;3:1545-1558
69. Xu J, Nawaz Z, Tsai S, Tsai M-J, O'Malley B. The extreme C terminus of progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor. Proc Natl Acad Sci USA 1996;93:12195-12199
70. Smith C, O'Malley B. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004;25:45-71
71. McDonnell D, Wijayaratne A, Chang C-Y, Norris J. Elucidation of the molecular mechanism of action of selective estrogen receptor modulators. Am J Cardiol 2002;90:35F-43F
72. Giannoukos G, Szaparay D, Smith C, Meeker J, Simons SJ. New antiprogestins with partial agonist activity: potential selective progesterone receptor modulator (SPRMs) and probes for receptor and coregulator-induced changes in progesterone receptor induction properties. Mol Endocrinol 2001;15:255-270
73. Takimoto G, Graham J, Jackson T, et al. Tamoxifen resistant breast cancer: coregulators determine the direction of transcription by antagonist-occupied receptors. J Steroid Biochem Mol Biol 1999;69:45-50
74. Shang Y, Brown M. Molecular determinants for the tissue specificity of SERMs. Science 2002;295:2465-2468
75. Liu Z, Auboeuf D, Wong J, et al. Coactivator/corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486. Proc Natl Acad Sci USA 2002;99:7940-7944
76. Rogatsky I, Wang J-C, Derynck M, et al. Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor. Proc Natl Acad Sci USA 2003;100:13845-13850
77. Kraus W, McInerney E, Katzenellenbogen B. Ligand-dependent, transcriptionally productive association of the amino- and carboxyl-terminal regions of a steroid hormone nuclear receptor. Proc Natl Acad Sci USA 1995;92:12314-12318
78. Tora L, White J, Brou C, et al. The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell 1989;59:477-487
79. Weigel N. Steroid hormone receptors and their regulation by phosphorylation. Biochem J 1996;319:657-667
80. Rochette-Egly C. Nuclear receptors: integration of multiple signalling pathways through phosphorylation. Cell Signal 2003;15:355-366
81. Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman B. Direct coupling of trancription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell 2000;6:307-316
82. Auboeuf D, Dowhan D, Li X, et al. CoAA, a nuclear receptor coactivator protein at the interface of transcriptional coactivation and RNA splicing. Mol Cell Biol 2004;24:442-453
83. Auboeuf D, Honig A, Berget S, O'Malley B. Coordinate regulation of transcription and splicing by steroid receptor coregulators. Science 2002;298:416-419
84. Wu X, Li H, Chen J. The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor. J Biol Chem 2001;276:23962-23968
85. Kumar R, Lee J-C, Bolen D, Thompson E. The conformation of the glucocorticoid receptor AF1/tau1 domain induced by osmolyte binds co-regulatory proteins. J Biol Chem 2001;276:18146-18152
86. Lanz R, McKenna N, Onãte S, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 1999;97:17-27
87. Lanz R, Razani B, Goldberg A, O'Malley B. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA coactivator. Proc Natl Acad Sci USA 2002;99:16081-16086
88. Endoh H, Maruyama K, Masuhiro Y, et al. Purification and identification of p68 helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor α. Mol Cell Biol 1999;19:5363-5372
89. Wansa K, Harris J, Yan G, Ordentlich P, Muscat G. The AF-1 domain of the orphan nuclear receptor NOR-1 mediates trans-activation, coactivator recruitment, and activation by the purine anti-metabolite 6-mercaptopurine. J Biol Chem 2003;278:24776-24790
90. Wansa K, Harris J, Muscat G. The activation function-1 domain of Nur77/NR4A1 mediates trans-activation, cell specificity, and coactivator recruitment. J Biol Chem 2002;277:33001-33011
91. Callewaert L, Verrijdt G, Christiaens V, Haelens A, Claessens F. Dual function of an amino-terminal amphipathic helix in androgen receptor-mediated transactivation through specific and non-specific response elements. J Biol Chem 2003;278:8212-8218
92. Wallberg A, Neely K, Gustafsson J-A, Workman J, Wright A, Grant P. Histone acetyltransferase complexes can mediate transcriptional activation by the major glucocorticoid receptor activation domain. Mol Cell Biol 1999;19:5952-5959
93. Ma H, Hong H, Huang S-M, et al. Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins. Mol Cell Biol 1999;19:6164-6173
94. Onãte S, Boonyaratanakornkit V, Spencer T, et al. The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors. J Biol Chem 1998;273:12101-12108
95. Alen P, Claessens F, Verhoeven G, Rombauts W, Peeters B. The androgen receptor amino-terminal domain plays a key role in p160 coactivator-stimulated gene transcription. Mol Cell Biol 1999;19:6085-6097
96. Webb P, Nguyen P, Shinsako J, et al. Estrogen receptor activation function 1 works by binding p160 coactivator proteins. Mol Endocrinol 1998;12:1605-1618
97. Bommer M, Benecke A, Gronemeyer H, Rochette-Egly C. TIF2 mediates the synergy between RARαI activation functions AF-1 and AF-2. J Biol Chem 2002;277:37961-37966
98. Hittelman A, Burakov D, Ineguez-Lluhi J, Freedman L, Garabedian M. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBOJ 1999;18:5380-5388
99. Reid R, Kelly S, Watt K, Price N, McEwan I. Conformational analysis of the androgen receptor amino-terminal domain involved in transactivation. J Biol Chem 2002;277:20079-20086
100. Baskakov I, Kumar R, Srinivasan G, Ji Y-S, Bolen D, Thompson E. Trimethylamine N-oxide-induced cooperative folding of am intrinsically unfolded transcription-activating fragment of human glucocorticoid receptor. J Biol Chem 1999;274:10693-10696
101. Warnmark A, Wikstrom A, Wright A, Gustafsson J-A, Hard T. The N-terminal regions of estrogen receptor alpha and beta are unstructured and show different TBP binding properties. J Biol Chem 2001;276:45939-45944
102. Shen F, Triezenberg S, Hensley P, Porter D, Knutson J. Transcriptional activation domain of the herpesvirus protein VP16 becomes conformationally constrained upon interaction with basal transcription factors. J Biol Chem 1996;271:4827-4837
103. Radhakrishnan I, Perez-Alvarado G, Parker D, Dyson H, Montminy M, Wright P. Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions. Cell 1997;91:741-752
104. Schmitz M, dos Santos Silva M, Altmann H, Czisch M, Holak T, Baeuerle P. Structural and functional analysis of the NF-κB p65 C terminus. J Biol Chem 1994;269:25613-25620
105. Folkers G, van Heerde E, van der Saag P. Activation function 1 of retinoic acid receptor β2 is an acidic activator resembling VP16. J Biol Chem 1995;270:23552-23559
106. Bain D, Franden M, McManaman J, Takimoto G, Horwitz K. The N-terminal region of the human progesterone A-receptor. J Biol Chem 2000;275:7313-7320
107. Bain D, Franden M, McManaman J, Takimoto G, Horwitz K. The N-terminal region of human progesterone B-receptors. J Biol Chem 2001;276:23825-23831
108. Meyer M-E, Quirin-Stricker C, Lerouge T, Bocquel M-T, Gronemeyer H. A limiting factor mediates the differential activation of promoters by the human progesterone receptor isoforms. J Biol Chem 1992;267:10882-10887
109. Sartorius C, Melville M, Hovland A, Tung L, Takimoto G, Horwitz K. A third transactivation function (AF3) of human progesterone receptors located in the unique N-terminal segment of the B-isoform. Mol Endocrinol 1994;8:1347-1360
110. Takimoto G, Tung L, Abdel-Hafiz H, et al. Functional properties of the N-terminal region of progesterone receptors and their mechanistic relationship to structure. J Steroid Biochem Mol Biol 2003;85:209-219
111. Abdel-Hafiz H, Takimoto G, Tung L, Horwitz K. The inhibitory function of human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression. J Biol Chem 2002;277:33950-33956
112. Huse B, Verca S, Matthey P, Rusconi S. Definition of a negative modulation domain in the human progesterone receptor. Mol Endocrinol 1998;12:1334-1342
113. McInerney E, Katzenellenbogen B. Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcriptional activation. J Biol Chem 1996;271:24172-24178
114. Chwalisz K, DeManno D, Garg R, Larsen L, Mattia-Goldberg C, Stickler T. Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata. Semin Reprod Med 2004;22:113-119
115. DeManno D, Elger W, Garg R, et al. Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids 2003;68:1019-1032
116. Dong Y, Rogberge J, Wang Z, et al. Characterization of a new class of selective nonsteroidal progesterone receptor agonists. Steroids 2004;69:201-217
117. Zhi L, Tegley C, Pio B, et al. Synthesis and biological activity of 5-methylidene 1,2-dihydrochromeno[3,4-f]quinoline derivatives as progesterone receptor modulators. Bioorg Med Chem 2003;13:2071-2074
118. Zhi L, Tegley C, Pio B, et al. 5-Benzylidene-1,2-dihydrochormeno[3,4-f] quinolines as selective progesterone receptor modulators. J Med Chem 2003;46:4104-4112
119. Mangal R, Wiehle R, Poindester AR, Weigel N. Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle. JSteroid Biochem Mol Biol 1997;63:195-202
120. Graham J, Yeates C, Balleine R, et al. Characterization of progesterone receptor A and B expression in human breast cancer. Cancer Res 1995;55:5063-5068