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Science 17 December 1999:
Vol. 286. no. 5448, pp. 2328 - 2331
DOI: 10.1126/science.286.5448.2328
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Reports

Postnatal Sex Reversal of the Ovaries in Mice Lacking Estrogen Receptors alpha  and beta  

J. F. Couse, 1 S. Curtis Hewitt, 1 D. O. Bunch, 2 M. Sar, 3 V. R. Walker, 1 B. J. Davis, 4 K. S. Korach 1*

Mice lacking estrogen receptors alpha  and beta  were generated to clarify the roles of each receptor in the physiology of estrogen target tissues. Both sexes of alpha beta estrogen receptor knockout (alpha beta ERKO) mutants exhibit normal reproductive tract development but are infertile. Ovaries of adult alpha beta ERKO females exhibit follicle transdifferentiation to structures resembling seminiferous tubules of the testis, including Sertoli-like cells and expression of Müllerian inhibiting substance, sulfated glycoprotein-2, and Sox9. Therefore, loss of both receptors leads to an ovarian phenotype that is distinct from that of the individual ERKO mutants, which indicates that both receptors are required for the maintenance of germ and somatic cells in the postnatal ovary.

1 Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology,
4 Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
2 Laboratory of Reproductive Biology, Department of Cell Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3 Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
*   To whom correspondence should be addressed. E-mail: korach{at}niehs.nih.gov

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Reproductive Endocrinology and Toxicological Pathology over the Life Span of the Female Rodent.
B. J. Davis, G. Travlos, and T. McShane (2001)
Toxicol Pathol 29, 77-83
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Hormones in male sexual development.
S. Nef and L. F. Parada (2000)
Genes & Dev. 14, 3075-3086
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Another role highlighted for estrogens in the male: Sexual behavior.
E. R. Simpson and S. R. Davis (2000)
PNAS
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Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO).
S. Ogawa, A. E. Chester, S. C. Hewitt, V. R. Walker, J.-A. Gustafsson, O. Smithies, K. S. Korach, and D. W. Pfaff (2000)
PNAS
   Abstract »    Full Text »
Development of Peptide Antagonists That Target Estrogen Receptor {beta}-Coactivator Interactions.
J. M. Hall, C.-y. Chang, and D. P. McDonnell (2000)
Mol. Endocrinol. 14, 2010-2023
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Estrogen Receptor {alpha} Has a Functional Role in the Mouse Rete Testis and Efferent Ductules.
K.-H. Lee, R. A. Hess, J. M. Bahr, D. B. Lubahn, J. Taylor, and D. Bunick (2000)
Biol Reprod 63, 1873-1880
   Abstract »    Full Text »
Increased adipose tissue in male and female estrogen receptor-alpha knockout mice.
P. A. Heine, J. A. Taylor, G. A. Iwamoto, D. B. Lubahn, and P. S. Cooke (2000)
PNAS 97, 12729-12734
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The Differential Fate of Mesonephric Tubular-Derived Efferent Ductules in Estrogen Receptor-{alpha} Knockout Versus Wild-Type Female Mice.
C. S. Rosenfeld, P. S. Cooke, T. H. Welsh Jr., G. Simmer, M. G. Hufford, J.-A. Gustafsson, R. A. Hess, and D. B. Lubahn (2000)
Endocrinology 141, 3792-3798
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Ovarian Tumors in Rats Induced by Chronic 2,3,7,8-Tetrachlorodibenzo-p- Dioxin Treatment.
B. J. Davis, E. A. McCurdy, B. D. Miller, G. W. Lucier, and A. M. Tritscher (2000)
Cancer Res. 60, 5414-5419
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Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts.
M. B. Hawkins, J. W. Thornton, D. Crews, J. K. Skipper, A. Dotte, and P. Thomas (2000)
PNAS 97, 10751-10756
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Aromatase Inhibition in the Human Male Reveals a Hypothalamic Site of Estrogen Feedback.
F. J. Hayes, S. B. Seminara, S. DeCruz, P. A. Boepple, and W. F. Crowley Jr. (2000)
J. Clin. Endocrinol. Metab. 85, 3027-3035
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Induction of Mammary Gland Development in Estrogen Receptor-{alpha} Knockout Mice.
W. P. Bocchinfuso, J. K. Lindzey, S. C. Hewitt, J. A. Clark, P. H. Myers, R. Cooper, and K. S. Korach (2000)
Endocrinology 141, 2982-2994
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An Age-Related Ovarian Phenotype in Mice with Targeted Disruption of the Cyp 19 (Aromatase) Gene.
K. L. Britt, A. E. Drummond, V. A. Cox, M. Dyson, N. G. Wreford, M. E. E. Jones, E. R. Simpson, and J. K. Findlay (2000)
Endocrinology 141, 2614-2623
   Abstract »    Full Text »    PDF »
Chapter 8: Estrogen Receptor-Mediated Processes in Normal and Cancer Cells.
R. B. Dickson and G. M. Stancel (2000)
J Natl Cancer Inst Monographs 2000, 135-145
   Abstract »    Full Text »    PDF »


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