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Endocrine Reviews 18 (4): 502-519
Copyright © 1997 by The Endocrine Society

Physiological Action of Progesterone in Target Tissues1

J. Dinny Graham2 and Christine L. Clarke

Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead NSW 2145, Australia

I. Introduction
II. Synthesis and Secretion of Progesterone
III. The Progesterone Receptor
A. PR expression and regulation
IV. Progesterone Regulation of Gene Expression in the Uterus, Ovary, and Chick Oviduct
A. Progesterone effects on proliferation and decidualization in the uterus during the menstrual cycle
B. Progesterone regulation of insulin-like growth factor (IGF) pathways in the endometrium
C. Control of ovulation
D. Implantation, uterine proliferation, and early pregnancy
E. Myometrial contractility
F. Chick oviduct
V. Progesterone Action in the Breast
A. Effect of progesterone on proliferation of the normal breast
B. Progesterone regulation of genes associated with cell cycle progression
C. Progesterone regulation of growth factors and growth factor receptors in the breast
D. Markers of progestin action in the breast
E. Progesterone effects on lactation
VI. Progesterone Effects in the Brain
VII. Progesterone Effects on Bone
VIII. Antiestrogen Action of Progesterone
A. Inhibition of ER expression
B. Progesterone inhibition of the molecular action of ER
IX. Summary and Conclusion
X. Future Directions




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[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
J. Fahnenstich, A. Nandy, K. Milde-Langosch, T. Schneider-Merck, N. Walther, and B. Gellersen
Promyelocytic leukaemia zinc finger protein (PLZF) is a glucocorticoid- and progesterone-induced transcription factor in human endometrial stromal cells and myometrial smooth muscle cells
Mol. Hum. Reprod., October 1, 2003; 9(10): 611 - 623.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
B. Mulac-Jericevic, J. P. Lydon, F. J. DeMayo, and O. M. Conneely
Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform
PNAS, August 19, 2003; 100(17): 9744 - 9749.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. Crescioli, M. Maggi, G. B. Vannelli, P. Ferruzzi, S. Granchi, R. Mancina, M. Muratori, G. Forti, M. Serio, and M. Luconi
Expression of Functional Estrogen Receptors in Human Fetal Male External Genitalia
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1815 - 1824.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
X. Cui, P. Zhang, W. Deng, S. Oesterreich, Y. Lu, G. B. Mills, and A. V. Lee
Insulin-Like Growth Factor-I Inhibits Progesterone Receptor Expression in Breast Cancer Cells via the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Pathway: Progesterone Receptor as a Potential Indicator of Growth Factor Activity in Breast Cancer
Mol. Endocrinol., April 1, 2003; 17(4): 575 - 588.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
R. Shao, E. Markstrom, P. A. Friberg, M. Johansson, and H. Billig
Expression of Progesterone Receptor (PR) A and B Isoforms in Mouse Granulosa Cells: Stage-Dependent PR-Mediated Regulation of Apoptosis and Cell Proliferation
Biol Reprod, March 1, 2003; 68(3): 914 - 921.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
D. D. Baird, C. R. Weinberg, D. R. McConnaughey, and A. J. Wilcox
Rescue of the Corpus Luteum in Human Pregnancy
Biol Reprod, February 1, 2003; 68(2): 448 - 456.
[Abstract] [Full Text] [PDF]

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 Recent Prog Horm ResHome page
Y. Wan and S. K. Nordeen
Overlapping but Distinct Profiles of Gene Expression Elicited by Glucocorticoids and Progestins
Recent Prog. Horm. Res., January 1, 2003; 58(1): 199 - 226.
[Abstract] [Full Text] [PDF]

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 Reproductive SciencesHome page
E. Smid-Koopman, L. J. Blok, L. C. M. Kuhne,, C. W. Burger, T. J. M. Helmerhorst, A. O. Brinkman, and F. J. Huikeshoven
Distinct Functional Differences of Human Progesterone Receptors A and B on Gene Expression and Growth Regulation in Two Endometrial Carcinoma Cell Lines
Reproductive Sciences, January 1, 2003; 10(1): 49 - 57.
[Abstract] [PDF]

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 EndocrinologyHome page
T. M. Ahola, T. Manninen, N. Alkio, and T. Ylikomi
G Protein-Coupled Receptor 30 Is Critical for a Progestin-Induced Growth Inhibition in MCF-7 Breast Cancer Cells
Endocrinology, September 1, 2002; 143(9): 3376 - 3384.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
P. A. Newcomb, L. Titus-Ernstoff, K. M. Egan, A. Trentham-Dietz, J. A. Baron, B. E. Storer, W. C. Willett, and M. J. Stampfer
Postmenopausal Estrogen and Progestin Use in Relation to Breast Cancer Risk
Cancer Epidemiol. Biomarkers Prev., July 1, 2002; 11(7): 593 - 600.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Y. Wan and S. K. Nordeen
Overlapping but Distinct Gene Regulation Profiles by Glucocorticoids and Progestins in Human Breast Cancer Cells
Mol. Endocrinol., June 1, 2002; 16(6): 1204 - 1214.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
A. B. Spurdle, J. L. Hopper, X. Chen, M. R. E. McCredie, G. G. Giles, D. J. Venter, M. C. Southey, and G. Chenevix-Trench
The Progesterone Receptor Exon 4 Val660Leu G/T Polymorphism and Risk of Breast Cancer in Australian Women
Cancer Epidemiol. Biomarkers Prev., May 1, 2002; 11(5): 439 - 443.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
C.L. Swan, M.C. Agostini, P.M. Bartlewski, V. Feyles, R.J. Urban, and P.J. Chedrese
Effects of Progestins on Progesterone Synthesis in a Stable Porcine Granulosa Cell Line: Control of Transcriptional Activity of the Cytochrome P450 Side-Chain Cleavage Gene
Biol Reprod, April 1, 2002; 66(4): 959 - 965.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
C.-L. Chen, N. S. Weiss, P. Newcomb, W. Barlow, and E. White
Hormone Replacement Therapy in Relation to Breast Cancer
JAMA, February 13, 2002; 287(6): 734 - 741.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Dai, D. M. Wolf, E. S. Litman, M. J. White, and K. K. Leslie
Progesterone Inhibits Human Endometrial Cancer Cell Growth and Invasiveness: Down-Regulation of Cellular Adhesion Molecules through Progesterone B Receptors
Cancer Res., February 1, 2002; 62(3): 881 - 886.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
C. Rodriguez-Sallaberry, F. A. Simmen, and R. C.M. Simmen
Polyamine- and Insulin-Like Growth Factor-I-Mediated Proliferation of Porcine Uterine Endometrial Cells: A Potential Role for Spermidine/Spermine N1-Acetyltransferase During Peri-Implantation
Biol Reprod, August 1, 2001; 65(2): 587 - 594.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
R. L. Arnett-Mansfield, A. deFazio, G. V. Wain, R. C. Jaworski, K. Byth, P. A. Mote, and C. L. Clarke
Relative Expression of Progesterone Receptors A and B in Endometrioid Cancers of the Endometrium
Cancer Res., June 1, 2001; 61(11): 4576 - 4582.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Y. Wan, K. K. Coxe, V. G. Thackray, P. R. Housley, and S. K. Nordeen
Separable Features of the Ligand-Binding Domain Determine the Differential Subcellular Localization and Ligand-Binding Specificity of Glucocorticoid Receptor and Progesterone Receptor
Mol. Endocrinol., January 1, 2001; 15(1): 17 - 31.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
T. Kurita, K.-j. Lee, P. T.K. Saunders, P. S. Cooke, J. A. Taylor, D. B. Lubahn, C. Zhao, S. Mäkelä, J.-A. Gustafsson, R. Dahiya, et al.
Regulation of Progesterone Receptors and Decidualization in Uterine Stroma of the Estrogen Receptor-{{alpha}} Knockout Mouse
Biol Reprod, January 1, 2001; 64(1): 272 - 283.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. Mayerhofer, S. Fritz, R. Grünert, S. L. Sanders, D. M. Duffy, S. R. Ojeda, and R. L. Stouffer
D1-Receptor, DARPP-32, and PP-1 in the Primate Corpus Luteum and Luteinized Granulosa Cells: Evidence for Phosphorylation of DARPP-32 by Dopamine and Human Chorionic Gonadotropin
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4750 - 4757.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
H. Okada, T. Nakajima, M. Sanezumi, A. Ikuta, K. Yasuda, and H. Kanzaki
Progesterone Enhances Interleukin-15 Production in Human Endometrial Stromal Cells in Vitro
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4765 - 4770.
[Abstract] [Full Text]

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 EndocrinologyHome page
N. Danilovich, P. S. Babu, W. Xing, M. Gerdes, H. Krishnamurthy, and M. R. Sairam
Estrogen Deficiency, Obesity, and Skeletal Abnormalities in Follicle-Stimulating Hormone Receptor Knockout (FORKO) Female Mice
Endocrinology, November 1, 2000; 141(11): 4295 - 4308.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Runic, F. Schatz, L. Wan, R. Demopoulos, G. Krikun, and C. J. Lockwood
Effects of Norplant on Endometrial Tissue Factor Expression and Blood Vessel Structure
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3853 - 3859.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
D. C. Skinner, T. G. Harris, and N. P. Evans
Duration and Amplitude of the Luteal Phase Progesterone Increment Times the Estradiol-Induced Luteinizing Hormone Surge in Ewes
Biol Reprod, October 1, 2000; 63(4): 1135 - 1142.
[Abstract] [Full Text]

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 ScienceHome page
B. Mulac-Jericevic, R. A. Mullinax, F. J. DeMayo, J. P. Lydon, and O. M. Conneely
Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone Receptor-B Isoform
Science, September 8, 2000; 289(5485): 1751 - 1754.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
C. L. Smith, R. G. Wolford, T. B. O’Neill, and G. L. Hager
Characterization of Transiently and Constitutively Expressed Progesterone Receptors: Evidence for Two Functional States
Mol. Endocrinol., July 1, 2000; 14(7): 956 - 971.
[Abstract] [Full Text]

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 Toxicol SciHome page
J. C. O'Connor, L. G. Davis, S. R. Frame, and J. C. Cook
Evaluation of a Tier I Screening Battery for Detecting Endocrine-Active Compounds (EACs) Using the Positive Controls Testosterone, Coumestrol, Progesterone, and RU486
Toxicol. Sci., April 1, 2000; 54(2): 338 - 354.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
T. Kurita, K.-j. Lee, P. S. Cooke, J. A. Taylor, D. B. Lubahn, and G. R. Cunha
Paracrine Regulation of Epithelial Progesterone Receptor by Estradiol in the Mouse Female Reproductive Tract
Biol Reprod, April 1, 2000; 62(4): 821 - 830.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
V. C.-L. Lin, E. H. Ng, S. E. Aw, M. G.-K. Tan, E. H.-L. Ng, and B. H. Bay
Progesterone Induces Focal Adhesion in Breast Cancer Cells MDA-MB-231 Transfected with Progesterone Receptor Complementary DNA
Mol. Endocrinol., March 1, 2000; 14(3): 348 - 358.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
T. N. Seagroves, J. P. Lydon, R. C. Hovey, B. K. Vonderhaar, and J. M. Rosen
C/EBP{beta} (CCAAT/Enhancer Binding Protein) Controls Cell Fate Determination during Mammary Gland Development
Mol. Endocrinol., March 1, 2000; 14(3): 359 - 368.
[Abstract] [Full Text]

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 Biol. Reprod.Home page
G. A. Johnson, T. E. Spencer, R. C. Burghardt, M. M. Joyce, and F. W. Bazer
Interferon-Tau and Progesterone Regulate Ubiquitin Cross-Reactive Protein Expression in the Ovine Uterus
Biol Reprod, March 1, 2000; 62(3): 622 - 627.
[Abstract] [Full Text]

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 Reproductive SciencesHome page
C. M. Peterson
Estrogen and Progesterone Receptors: An Overview From the Year 2000
Reproductive Sciences, January 1, 2000; 7(1_suppl): S3 - S7.
[Abstract] [PDF]

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 EndocrinologyHome page
C. Ko, Y.-H. In, and O.-K. Park-Sarge
Role of Progesterone Receptor Activation in Pituitary Adenylate Cyclase Activating Polypeptide Gene Expression in Rat Ovary
Endocrinology, November 1, 1999; 140(11): 5185 - 5194.
[Abstract] [Full Text]


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