OVARY-INTACT, BUT NOT OVARIECTOMIZED FEMALE ACI RATS TREATED WITH 17-BETA-ESTRADIOL RAPIDLY DEVELOP MAMMARY-CARCINOMA

We have examined the ability of 17 beta-estradiol (E2) to induce devel opment of mammary cancers in the female ACI rat, Continuous treatment with E2, delivered through release from s.c. Silastic tubing implants containing 27.5 mg crystalline hormone, resulted in rapid development of palpable mammary tumors in ovary-intact ACI rats, In a population o f 21 E2-treated rats, palpable tumors were first observed following 99 days treatment and 100% of the treated population developed tumors wi thin 197 days, The median and mean times to appearance of first palpab le tumor were 143 and 145 days respectively, All mammary tumors were c lassified as carcinomas and invasive features were observed, Circulati ng E2 levels in the treated animals at the time of sacrifice averaged 185 pg/ml serum, Mammary tumors were not observed in ovary-intact fema le ACI rats that were not treated with E2, This is the first report in dicating that this naturally occurring estrogen is capable of inducing mammary cancers in the ACI rat strain, Mammary carcinoma did not deve lop in a population of 11 ovariectomized female ACI rats treated with E2 for a period of 140 days, Circulating E2 levels in the treated ovar iectomized animals averaged 207 pg/ml, These data indicate that the ov ary modulates estrogen-mediated mammary carcinogenesis in this rat str ain, Both ovary-intact and ovariectomized female ACI rats displayed si milar susceptibilities to E2-induced pituitary tumors and hyperprolact inemia, Pituitary weight was increased 6.0-fold in ovary-intact ACI ra ts and 5.3-fold in ovariectomized female rats, Circulating prolactin l evels averaged 2318 ng/ml in E2-treated, ovary-intact rats and 2285 ng /ml in E2-treated, ovariectomized ACI rats, These data indicate that e strogen-induced hyperprolactinemia is not the sole factor leading to d evelopment of mammary cancers in the E2-treated ACI rat.