This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by GRECO, T. L. Articles by GORSKI, J. Search for Related Content PubMed PubMed Citation Articles by GRECO, T. L. Articles by GORSKI, J.

Estrogen Receptors, Estradiol, and Diethylstilbestrol in Early Development: The Mouse as a Model for the Study of Estrogen Receptors and Estrogen Sensitivity in Embryonic Development of Male and Female Reproductive Tracts^*

TAMARA L. GRECO, THERESA M. DUELLO and JACK GORSKI

Department of Biochemistry and Animal Science, University of Wisconsin-Madison Madison, Wisconsin 53706
Department of Obstetrics and Gynecology, University of Wisconsin-Madison Madison, Wisconsin 53706

Correspondence: Address requests for reprints to: Jack Gorski, Ph.D, Department of Biochemistry, University of Wisconsin-Madison, 420 Henry Mall, Madison, Wisconsin 53706–1569.

Abstract

I. Introduction: DIETHYLSTILBESTROL (DES), a potent estrogen, once thought to be effective in preventing first trimester miscarriages, was administered in the 1950s to a population of pregnant women who were considered to be at risk (1, 2). A generation later, an increase in cases of a rare form of vaginal adenocarcinoma in girls when they reached puberty led Herbst and co-workers (3, 4) to suggest a link between prenatal exposure to DES and this cancer. There was widespread use of DES for maintenance of pregnancies between the years 1945–1971, and it has been estimated that 980,000 to 4.5 million boys and girls born during those years were exposed to DES in utero (5). For example, the annual incidence rate of genital cancer (per 10,000,000) for 16-yr-old white females born in 1955 was 17.8 as compared to 0 for 16-yr-old girls born in 1949 (4). In addition to the neoplasia, benign anomalies were also reported in women exposed to DES in utero (6–8).

Footnotes

^* Supported in part by NIH Grants HD-08192 and HD-07259, by USDA Grant 8901604, and by a grant from the National Foundation for Cancer Research (to J.G.).

Current address: Steroid Research Unit, Department of Obstetrics and Gynecology, The University of Michigan, Ann Arbor, Michigan 48109–0278.

This article has been cited by other articles:

				C. Montani, M. Penza, M. Jeremic, G. Biasiotto, G. La Sala, M. De Felici, P. Ciana, A. Maggi, and D. Di Lorenzo Genistein is an Efficient Estrogen in the Whole-Body throughout Mouse Development Toxicol. Sci., May 1, 2008; 103(1): 57 - 67. [Abstract] [Full Text] [PDF]

				C A Wilson and D C Davies The control of sexual differentiation of the reproductive system and brain Reproduction, February 1, 2007; 133(2): 331 - 359. [Abstract] [Full Text] [PDF]

				T. Simoncini, C. Scorticati, P. Mannella, A. Fadiel, M. S. Giretti, X.-D. Fu, C. Baldacci, S. Garibaldi, A. Caruso, L. Fornari, et al. Estrogen Receptor {alpha} Interacts with G{alpha}13 to Drive Actin Remodeling and Endothelial Cell Migration via the RhoA/Rho Kinase/Moesin Pathway Mol. Endocrinol., August 1, 2006; 20(8): 1756 - 1771. [Abstract] [Full Text] [PDF]

				S.-M. Ho, W.-Y. Tang, J. Belmonte de Frausto, and G. S. Prins Developmental Exposure to Estradiol and Bisphenol A Increases Susceptibility to Prostate Carcinogenesis and Epigenetically Regulates Phosphodiesterase Type 4 Variant 4 Cancer Res., June 1, 2006; 66(11): 5624 - 5632. [Abstract] [Full Text] [PDF]

				Y. Li, P. J. Friel, D. J. McLean, and M. D. Griswold Cystatin E1 and E2, New Members of Male Reproductive Tract Subgroup Within Cystatin Type 2 Family Biol Reprod, August 1, 2003; 69(2): 489 - 500. [Abstract] [Full Text] [PDF]

				M. Jakacka, M. Ito, F. Martinson, T. Ishikawa, E. J. Lee, and J. L. Jameson An Estrogen Receptor (ER){alpha} Deoxyribonucleic Acid-Binding Domain Knock-In Mutation Provides Evidence for Nonclassical ER Pathway Signaling in Vivo Mol. Endocrinol., October 1, 2002; 16(10): 2188 - 2201. [Abstract] [Full Text] [PDF]

				M. Yoshida, A. Takenaka, S.-I. Katsuda, Y. Kurokawa, and A. Maekawa Neonatal Exposure to p-tert-octylphenol Causes Abnormal Expression of Estrogen Receptor {alpha} and Subsequent Alteration of Cell Proliferating Activity in the Developing Donryu Rat Uterus Toxicol Pathol, April 1, 2002; 30(3): 357 - 364. [Abstract] [PDF]

				G. J. Pepe, R. B. Billiar, M. G. Leavitt, N. C. Zachos, J. A. Gustafsson, and E. D. Albrecht Expression of Estrogen Receptors {alpha} and {beta} in the Baboon Fetal Ovary Biol Reprod, April 1, 2002; 66(4): 1054 - 1060. [Abstract] [Full Text] [PDF]

				J. J. Li, S. J. Weroha, M. F. Davis, O. Tawfik, X. Hou, and S. A. Li ER and PR in Renomedullary Interstitial Cells During Syrian Hamster Estrogen-Induced Tumorigenesis: Evidence for Receptor-Mediated Oncogenesis Endocrinology, September 1, 2001; 142(9): 4006 - 4014. [Abstract] [Full Text] [PDF]

				X. Li, E. Nokkala, W. Yan, T. Streng, N. Saarinen, A. Warri, I. Huhtaniemi, R. Santti, S. Makela, and M. Poutanen Altered Structure and Function of Reproductive Organs in Transgenic Male Mice Overexpressing Human Aromatase Endocrinology, June 1, 2001; 142(6): 2435 - 2442. [Abstract] [Full Text] [PDF]

				G. B. Tremblay, T. Kunath, D. Bergeron, L. Lapointe, C. Champigny, J.-A. Bader, J. Rossant, and V. Giguère Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR{beta} Genes & Dev., April 1, 2001; 15(7): 833 - 838. [Abstract] [Full Text]

				W. N. Jefferson, J. F. Couse, E. P. Banks, K. S. Korach, and R. R. Newbold Expression of Estrogen Receptor {beta} Is Developmentally Regulated in Reproductive Tissues of Male and Female Mice Biol Reprod, February 1, 2000; 62(2): 310 - 317. [Abstract] [Full Text]

				J. F. Couse, S. C. Hewitt, D. O. Bunch, M. Sar, V. R. Walker, B. J. Davis, and K. S. Korach Postnatal Sex Reversal of the Ovaries in Mice Lacking Estrogen Receptors  and   Science, December 17, 1999; 286(5448): 2328 - 2331. [Abstract] [Full Text]

				J. F. Couse and K. S. Korach Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us? Endocr. Rev., June 1, 1999; 20(3): 358 - 417. [Abstract] [Full Text]

				R. J. Roper, J. S. Griffith, C. R. Lyttle, R. W. Doerge, A. W. McNabb, R. E. Broadbent, and C. Teuscher Interacting Quantitative Trait Loci Control Phenotypic Variation in Murine Estradiol-Regulated Responses Endocrinology, February 1, 1999; 140(2): 556 - 561. [Abstract] [Full Text]

				A. M. M. van Pelt, D. G. de Rooij, B. van der Burg, P. T. van der Saag, J.-A. Gustafsson, and G. G. J. M. Kuiper Ontogeny of Estrogen Receptor-{beta} Expression in Rat Testis Endocrinology, January 1, 1999; 140(1): 478 - 483. [Abstract] [Full Text]

				J. A. Visser, A. McLuskey, M. Verhoef-Post, P. Kramer, J. A. Grootegoed, and A. P. N. Themmen Effect of Prenatal Exposure to Diethylstilbestrol on Mullerian Duct Development in Fetal Male Mice Endocrinology, October 1, 1998; 139(10): 4244 - 4251. [Abstract] [Full Text] [PDF]

				G. G. J. M. Kuiper, J. G. Lemmen, B. Carlsson, J. C. Corton, S. H. Safe, P. T. van der Saag, B. van der Burg, and J.-A. Gustafsson Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor {beta} Endocrinology, October 1, 1998; 139(10): 4252 - 4263. [Abstract] [Full Text] [PDF]

				P. S. Cooke, D. L. Buchanan, P. Young, T. Setiawan, J. Brody, K. S. Korach, J. Taylor, D. B. Lubahn, and G. R. Cunha Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium PNAS, June 10, 1997; 94(12): 6535 - 6540. [Abstract] [Full Text] [PDF]

				W. P. Bocchinfuso and K. S. Korach Estrogen Receptor Residues Required for Stereospecific Ligand Recognition and Activation Mol. Endocrinol., May 1, 1997; 11(5): 587 - 594. [Abstract] [Full Text]