Other precocious events occur in the prepubertal hamster uterus following neonatal DES, but not E2, treatment. One such event, reported previously and confirmed in the present study, is the development of pseudostratification in the columnar epithelium of the endometrial lumen. Another is the development of invaginating endometrial glands. More recently, we also detected precocious induction of the progesterone-receptor protein in the prepubertal hamster uterus following neonatal DES exposure. Although those events are considered to be abnormal when they occur before puberty, they are some of the most well-established responses to estrogen stimulation of the normal, adult reproductive tract.
The obvious implication is that the ultimate disruptive consequences of neonatal DES exposure are mediated by a functional ER system in the hamster’s early, developing reproductive tract. Indeed, similar levels of ERa protein were detected in control and neonatally DES-exposed uteri from 5-day-old hamsters. So, the inherent estrogenicity of DES may not be the sole determinant of its action as a perinatal ED agent, but it is a necessary one. This conclusion is supported by the extensive clinical and experimental evidence that perinatal DES-induced teratogenesis and neoplasia are confined to estrogen target tissues.