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Development, Vol 127, Issue 19 4277-4291, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes

S Dupont, A Krust, A Gansmuller, A Dierich, P Chambon and M Mark
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, College de France, BP 163, France.

The functions of estrogen receptors (ERs) in mouse ovary and genital tracts were investigated by generating null mutants for ERalpha (ERalphaKO), ERbeta (ERbetaKO) and both ERs (ERalphabetaKO). All ERalphaKO females are sterile, whereas ERbetaKO females are either infertile or exhibit variable degrees of subfertility. Mast cells present in adult ERalphaKO and ERalphabetaKO ovaries could participate in the generation of hemorrhagic cysts. Folliculogenesis proceeds normally up to the large antral stage in both ERalphaKO and ERbetaKO adults, whereas large antral follicles of ERalpha+/-ERbetaKO and ERalphabetaKO adults are markedly deficient in granulosa cells. Similarly, prematurely developed follicles found in prepubertal ERalphaKO ovaries appear normal, but their ERalphabetaKO counterparts display only few granulosa cell layers. Upon superovulation treatment, all prepubertal ERalphaKO females form numerous preovulatory follicles of which the vast majority do not ovulate. The same treatment fails to elicit the formation of preovulatory follicles in half of the ERbetaKO mice and in all ERalpha+/-/ERbetaKO mice. These and other results reveal a functional redundancy between ERalpha and ERbeta for ovarian folliculogenesis, and strongly suggest that (1) ERbeta plays an important role in mediating the stimulatory effects of estrogens on granulosa cell proliferation, (2) ERalpha is not required for follicle growth under wild type conditions, while it is indispensable for ovulation, and (3) ERalpha is also necessary for interstitial glandular cell development. Our data also indicate that ERbeta exerts some function in ERalphaKO uterus and vagina. ERalphabetaKO granulosa cells localized within degenerating follicles transform into cells displaying junctions that are unique to testicular Sertoli cells. From the distribution pattern of anti-Mullerian hormone (AMH) in ERalphabetaKO ovaries, it is unlikely that an elevated AMH level is the cause of Sertoli cell differentiation. Our results also show that cell proliferation in the prostate and urinary bladder of old ERbetaKO and ERalphabetaKO males is apparently normal.
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Development of Primordial Follicles in the Hamster: Role of Estradiol-17{beta}
Endocrinology, April 1, 2007; 148(4): 1707 - 1716.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
F. A. Syed, D. G. Fraser, T. C. Spelsberg, C. J. Rosen, A. Krust, P. Chambon, J. L. Jameson, and S. Khosla
Effects of Loss of Classical Estrogen Response Element Signaling on Bone in Male Mice
Endocrinology, April 1, 2007; 148(4): 1902 - 1910.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
L. Ciarloni, S. Mallepell, and C. Brisken
Amphiregulin is an essential mediator of estrogen receptor {alpha} function in mammary gland development
PNAS, March 27, 2007; 104(13): 5455 - 5460.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. L. Cho, S. H. Javid, A. M. Carothers, M. Redston, and M. M. Bertagnolli
Estrogen Receptors {alpha} and {beta} Are Inhibitory Modifiers of Apc-Dependent Tumorigenesis in the Proximal Colon of Min/+ Mice
Cancer Res., March 1, 2007; 67(5): 2366 - 2372.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. M. Corbacho, J. P. Eiserich, L. A. Zuniga, G. Valacchi, and A. C. Villablanca
Compromised Aortic Vasoreactivity in Male Estrogen Receptor-{alpha}-Deficient Mice during Acute Lipopolysaccharide-Induced Inflammation
Endocrinology, March 1, 2007; 148(3): 1403 - 1411.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
S. Kousteni, M. Almeida, L. Han, T. Bellido, R. L. Jilka, and S. C. Manolagas
Induction of Osteoblast Differentiation by Selective Activation of Kinase-Mediated Actions of the Estrogen Receptor
Mol. Cell. Biol., February 15, 2007; 27(4): 1516 - 1530.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
H. A. Harris
Estrogen Receptor-{beta}: Recent Lessons from in Vivo Studies
Mol. Endocrinol., January 1, 2007; 21(1): 1 - 13.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Penza, C. Montani, A. Romani, P. Vignolini, B. Pampaloni, A. Tanini, M. L. Brandi, P. Alonso-Magdalena, A. Nadal, L. Ottobrini, et al.
Genistein Affects Adipose Tissue Deposition in a Dose-Dependent and Gender-Specific Manner
Endocrinology, December 1, 2006; 147(12): 5740 - 5751.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
H. Hamada, M. K. Kim, A. Iwakura, M. Ii, T. Thorne, G. Qin, J. Asai, Y. Tsutsumi, H. Sekiguchi, M. Silver, et al.
Estrogen Receptors {alpha} and {beta} Mediate Contribution of Bone Marrow-Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction
Circulation, November 21, 2006; 114(21): 2261 - 2270.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. E. O'Brien, T. J. Peterson, M. H. Tong, E.-J. Lee, L. E. Pfaff, S. C. Hewitt, K. S. Korach, J. Weiss, and J. L. Jameson
Estrogen-induced Proliferation of Uterine Epithelial Cells Is Independent of Estrogen Receptor {alpha} Binding to Classical Estrogen Response Elements
J. Biol. Chem., September 8, 2006; 281(36): 26683 - 26692.
[Abstract] [Full Text] [PDF]

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 Hum Reprod UpdateHome page
K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws
Ovarian follicle development and transgenic mouse models
Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Poutanen
Toward understanding the endocrine regulation of gonadal somatic cells.
Endocrinology, August 1, 2006; 147(8): 3662 - 3665.
[Full Text] [PDF]

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 EndocrinologyHome page
J. F. Couse, M. M. Yates, K. F. Rodriguez, J. A. Johnson, D. Poirier, and K. S. Korach
The Intraovarian Actions of Estrogen Receptor-{alpha} Are Necessary to Repress the Formation of Morphological and Functional Leydig-Like Cells in the Female Gonad
Endocrinology, August 1, 2006; 147(8): 3666 - 3678.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
M. Pannetier, S. Fabre, F. Batista, A. Kocer, L. Renault, G. Jolivet, B. Mandon-Pepin, C. Cotinot, R. Veitia, and E. Pailhoux
FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development.
J. Mol. Endocrinol., June 1, 2006; 36(3): 399 - 413.
[Abstract] [Full Text] [PDF]

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J. Qiu, M. A. Bosch, S. C. Tobias, A. Krust, S. M. Graham, S. J. Murphy, K. S. Korach, P. Chambon, T. S. Scanlan, O. K. Ronnekleiv, et al.
A G-Protein-Coupled Estrogen Receptor Is Involved in Hypothalamic Control of Energy Homeostasis
J. Neurosci., May 24, 2006; 26(21): 5649 - 5655.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. C. Hewitt, J. Collins, S. Grissom, K. Hamilton, and K. S. Korach
Estren Behaves as a Weak Estrogen Rather than a Nongenomic Selective Activator in the Mouse Uterus
Endocrinology, May 1, 2006; 147(5): 2203 - 2214.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
S. J. Warden, L. K. Saxon, A. B. Castillo, and C. H. Turner
Knee ligament mechanical properties are not influenced by estrogen or its receptors
Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E1034 - E1040.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Ko, M. C. Gieske, L. Al-Alem, Y. Hahn, W. Su, M. C. Gong, M. Iglarz, and Y. Koo
Endothelin-2 in Ovarian Follicle Rupture
Endocrinology, April 1, 2006; 147(4): 1770 - 1779.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
C. J. Guigon and S. Magre
Contribution of Germ Cells to the Differentiation and Maturation of the Ovary: Insights from Models of Germ Cell Depletion
Biol Reprod, March 1, 2006; 74(3): 450 - 458.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Mallepell, A.ée Krust, P. Chambon, and C. Brisken
Paracrine signaling through the epithelial estrogen receptor {alpha} is required for proliferation and morphogenesis in the mammary gland
PNAS, February 14, 2006; 103(7): 2196 - 2201.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
H Watanabe, E Takahashi, M Kobayashi, M Goto, A Krust, P Chambon, and T Iguchi
The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor
J. Mol. Endocrinol., February 1, 2006; 36(1): 81 - 89.
[Abstract] [Full Text] [PDF]

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 ReproductionHome page
A. Roy and M. M Matzuk
Deconstructing mammalian reproduction: using knockouts to define fertility pathways
Reproduction, February 1, 2006; 131(2): 207 - 219.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. A Taylor, P. Cowin, J. F. Couse, K. S. Korach, and G. P. Risbridger
17{beta}-Estradiol Induces Apoptosis in the Developing Rodent Prostate Independently of ER{alpha} or ER{beta}
Endocrinology, January 1, 2006; 147(1): 191 - 200.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
Genetically Modified Animals in Endocrinology
Endocr. Rev., December 1, 2005; 26(7): 985 - 993.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
G. Vallejo, C. Ballare, J. Lino Baranao, M. Beato, and P. Saragueta
Progestin Activation of Nongenomic Pathways via Cross Talk of Progesterone Receptor with Estrogen Receptor {beta} Induces Proliferation of Endometrial Stromal Cells
Mol. Endocrinol., December 1, 2005; 19(12): 3023 - 3037.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Z. T. Ruiz-Cortes, S. Kimmins, L. Monaco, K. H. Burns, P. Sassone-Corsi, and B. D. Murphy
Estrogen Mediates Phosphorylation of Histone H3 in Ovarian Follicle and Mammary Epithelial Tumor Cells via the Mitotic Kinase, Aurora B
Mol. Endocrinol., December 1, 2005; 19(12): 2991 - 3000.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. F. Sneddon, N. Walther, and P. T. K. Saunders
Expression of Androgen and Estrogen Receptors in Sertoli Cells: Studies Using the Mouse SK11 Cell Line
Endocrinology, December 1, 2005; 146(12): 5304 - 5312.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
D. J. Lamb and L. Zhang
Challenges in Prostate Cancer Research: Animal Models for Nutritional Studies of Chemoprevention and Disease Progression
J. Nutr., December 1, 2005; 135(12): 3009S - 3015S.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
T. Baba, J. Mimura, N. Nakamura, N. Harada, M. Yamamoto, K.-i. Morohashi, and Y. Fujii-Kuriyama
Intrinsic Function of the Aryl Hydrocarbon (Dioxin) Receptor as a Key Factor in Female Reproduction
Mol. Cell. Biol., November 15, 2005; 25(22): 10040 - 10051.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
O. Imamov, G.-J. Shim, M. Warner, and J.-A. Gustafsson
Estrogen Receptor beta in Health and Disease
Biol Reprod, November 1, 2005; 73(5): 866 - 871.
[Abstract] [Full Text] [PDF]

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 J. Histochem. Cytochem.Home page
G. Pelletier, V. Luu-The, S. Li, and F. Labrie
Localization of Type 8 17{beta}-hydroxysteroid Dehydrogenase mRNA in Mouse Tissues as Studied by In Situ Hybridization
J. Histochem. Cytochem., October 1, 2005; 53(10): 1257 - 1271.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
K. L. Matthiesson, P. G. Stanton, L. O'Donnell, S. J. Meachem, J. K. Amory, R. Berger, W. J. Bremner, and R. I. McLachlan
Effects of Testosterone and Levonorgestrel Combined with a 5{alpha}-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist on Spermatogenesis and Intratesticular Steroid Levels in Normal Men
J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5647 - 5655.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
C Roger, S Lambard, A Bouskine, B Mograbi, D Chevallier, M Nebout, G Pointis, S Carreau, and P Fenichel
Estrogen-induced growth inhibition of human seminoma cells expressing estrogen receptor {beta} and aromatase
J. Mol. Endocrinol., August 1, 2005; 35(1): 191 - 199.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. K. Woodruff and K. E. Mayo
To {beta} or Not To {beta}: Estrogen Receptors and Ovarian Function
Endocrinology, August 1, 2005; 146(8): 3244 - 3246.
[Full Text] [PDF]

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 EndocrinologyHome page
J. F. Couse, M. M. Yates, B. J. Deroo, and K. S. Korach
Estrogen Receptor-{beta} Is Critical to Granulosa Cell Differentiation and the Ovulatory Response to Gonadotropins
Endocrinology, August 1, 2005; 146(8): 3247 - 3262.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. J. Guigon, N. Coudouel, S. Mazaud-Guittot, M. G. Forest, and S. Magre
Follicular Cells Acquire Sertoli Cell Characteristics after Oocyte Loss
Endocrinology, July 1, 2005; 146(7): 2992 - 3004.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
S. J Meachem, D. M Robertson, N. G Wreford, R. I McLachlan, and P. G Stanton
Oestrogen does not affect the restoration of spermatogenesis in the gonadotrophin-releasing hormone-immunised adult rat
J. Endocrinol., June 1, 2005; 185(3): 529 - 538.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. M. A. Emmen, J. F. Couse, S. A. Elmore, M. M. Yates, G. E. Kissling, and K. S. Korach
In Vitro Growth and Ovulation of Follicles from Ovaries of Estrogen Receptor (ER){alpha} and ER{beta} Null Mice Indicate a Role for ER{beta} in Follicular Maturation
Endocrinology, June 1, 2005; 146(6): 2817 - 2826.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
G. Soucy, G. Boivin, F. Labrie, and S. Rivest
Estradiol Is Required for a Proper Immune Response to Bacterial and Viral Pathogens in the Female Brain
J. Immunol., May 15, 2005; 174(10): 6391 - 6398.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
T. Korte, M. Fuchs, A. Arkudas, S. Geertz, R. Meyer, A. Gardiwal, G. Klein, M. Niehaus, A. Krust, P. Chambon, et al.
Female Mice Lacking Estrogen Receptor {beta} Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction
Circulation, May 10, 2005; 111(18): 2282 - 2290.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
E. R. Simpson, M. Misso, K. N. Hewitt, R. A. Hill, W. C. Boon, M. E. Jones, A. Kovacic, J. Zhou, and C. D. Clyne
Estrogen--the Good, the Bad, and the Unexpected
Endocr. Rev., May 1, 2005; 26(3): 322 - 330.
[Full Text] [PDF]

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 EndocrinologyHome page
G. Delbes, C. Levacher, C. Duquenne, C. Racine, P. Pakarinen, and R. Habert
Endogenous Estrogens Inhibit Mouse Fetal Leydig Cell Development via Estrogen Receptor {alpha}
Endocrinology, May 1, 2005; 146(5): 2454 - 2461.
[Abstract] [Full Text] [PDF]


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