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a Department of Biological Sciences, Wichita State University, Wichita, Kansas 67260-0026
b Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079
The synthetic estrogen diethylstilbestrol (DES) is a potent neonatal endocrine disruptor in the hamster. To test the specificity of this phenomenon, newborn animals were treated with 100 µg of either DES or the natural estrogen, estradiol-17ß (E2). Of the two, neonatal DES exposure caused greater morphological disruption throughout the female reproductive tract in prepubertal animals and in adults that either retained their ovaries or were ovariectomized and then given the same levels of chronic E2 stimulation. In the uterus, a characteristic histopathological profile, including enhancement of both hyperplastic and apoptotic activity, was initiated prepubertally and exclusively in the endometrial epithelial cell compartment from the neonatally DES-treated animals and then was promoted by E2 stimulation during adulthood. Interestingly, apoptotic activity was not detected in an area of endometrial epithelium that progressed to the neoplastic state in a DES-exposed animal. Lastly, chronic estrogen induction of lactoferrin was also restricted to the DES-exposed endometrium. We conclude that 1) DES is more active than E2 as a perinatal endocrine disruptor in the hamster and 2) this experimental system should be generally useful as a means to screen compounds for such activity and then probe their mechanism of action.
2 Correspondence: William J. Hendry III, Department of Biological Sciences, Wichita State University, 1845 Fairmount, Wichita, KS 672600026. FAX: 316 978 3772; hendry{at}wsuhub.uc.twsu.edu
3 Current address: Howard Hughes Medical Institute, Division of Hematology and Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8125, St. Louis, MO 631101093.
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