Differential activity of diethylstilbestrol versus estradiol as neonatal endocrine disrupters in the female hamster (Mesocricetus auratus) reproductive tract

The synthetic estrogen diethylstilbestrol (DES) is a potent neonatal endocrine disrupter in the hamster. To test the specificity of this phenomenon, newborn animals were treated with 100 mu g of either DES or the natural estrogen, estradiol-17 beta (E-2). 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 E-2 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 E-2 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 E-2 as a perinatal endocrine disrupter 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.