DURING DEVELOPMENT, 17-ALPHA-ESTRADIOL IS A POTENT ESTROGEN AND CARCINOGEN

Neonatal administration of estradiol-17 beta (E-2-17 beta) increases t he nuclear DNA content in the mouse reproductive tract. Similar respon ses have been demonstrated for synthetic estrogens such as diethylstil bestrol. One of the questions raised regarding environmental estrogens such as organochlorines is whether they are potent enough to result i n abnormal changes such as those demonstrated by both natural and synt hetic estrogens. To test this hypothesis, female BALB/c mice were trea ted neonatally (days 1-5) with either E-2-17 beta or estradiol-17 alph a (E-2-17 alpha), an inactive stereoisomer in adult reproductive tissu es. We also proposed whether neonatal administration of (E-2-17 alpha) was tumorigenic and whether the effects were age dependent. To answer these questions, one set each of 10-day-old treated and control mice received short-term secondary administration of E-2-17 beta, E-2-17 al pha, or cholesterol. Cervicovaginal tracts from intact BALB/c mice wer e examined histologically and by flow cytometry at 70 days of age and by histology alone at 18 to 22 months of age. The results include seve ral important findings: a) like E-2-17 beta, neonatal E-2-17 alpha tre atment induced persistent vaginal cornification, hypospadias, vaginal concreticns, and hyperproliferation in nearly 100% of the animals rega rdless of the secondary treatment for most groups; b) neonatal E-2-17 alpha treatment increased the nuclear DNA content of cervicovaginal ep ithelium at one-half both the level (mean DNA index of 1.02 vs 1.04) a nd incidence (22 vs 46% of the animals) of E-2-17 beta; c) short-term secondary treatment with E-2-17 alpha, unlike E-2-17 beta, did not sig nificantly augment the increase in DNA content (13% for E-2-17 alpha v s 37 and 56% for control and E-2-17 beta, respectively); and d) neonat al administration with E-2-17 alpha induced adenosquamous tumors in th e reproductive tract in 25% of the animals. Therefore, the biological effects (estrogenic potency) of E-2-17 alpha may be age dependent.