The relation of the dosage of diethylstilbestrol (DES) administered neonatally to the incidence and severity of genital tract and mammary gland lesions and to the levels of sex hormone receptors was examined using a mouse model for human intrauterine DES exposure. Female BALB/cCrgl mice received various doses of DES (ranging from 5 × 10-1–10-5 µg daily for the first 5 days of life) or the sesame oil vehicle alone. In the vagina, at all ages examined (1, 2, 6, and 12 months) cytosolic estrogen receptors are consistently decreased after high doses of neonatal DES (10-1 and 1 µg). In contrast, at the same ages, vaginal cytosolic progestin receptors increase after identical doses. In the uterus, the 1-µg dose of neonatal DES also consistently decreases cytosolic estrogen receptors while increasing cytosolic progestin receptors at 1, 2, and 6 months of age. Histologically, neonatal doses of 5 × 10-2 µg DES result in vaginal lesions at 2 months. With age, this threshold level decreases, implying interaction with an altered hormonal milieu. The uterus shows a sensitivity similar to that of the vagina in regard to the histopathological effects of neonatal DES. The ovary and mammary glands are 10- to 100-fold more sensitive to neonatal DES exposure.

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Supported by Grant CA05388, awarded by the National Cancer Institute, Department of Health and Human Services. Dedicated to the memory of Dr. Georges Rudali, eminent tumor biologist and great friend.

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