title: Ovary-intact, but not ovariectomized female ACI rats treated with 17beta-estradiol rapidly develop mammary carcinoma.
abstract: We have examined the ability of 17beta-estradiol (E2) to induce development 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 of 21 E2-treated rats, palpable tumors were first observed following 99 days treatment and 100% of the treated population developed tumors within 197 days. The median and mean times to appearance of first palpable tumor were 143 and 145 days respectively. All mammary tumors were classified as carcinomas and invasive features were observed. Circulating E2 levels in the treated animals at the time of sacrifice averaged 185 pg/ml serum. Mammary tumors were not observed in ovary-intact female ACI rats that were not treated with E2. This is the first report indicating that this naturally occurring estrogen is capable of inducing mammary cancers in the ACI rat strain. Mammary carcinoma did not develop in a population of 11 ovariectomized female ACI rats treated with E2 for a period of 140 days. Circulating E2 levels in the treated ovariectomized animals averaged 207 pg/ml. These data indicate that the ovary modulates estrogen-mediated mammary carcinogenesis in this rat strain. Both ovary-intact and ovariectomized female ACI rats displayed similar susceptibilities to E2-induced pituitary tumors and hyperprolactinemia. Pituitary weight was increased 6.0-fold in ovary-intact ACI rats and 5.3-fold in ovariectomized female rats. Circulating prolactin levels averaged 2318 ng/ml in E2-treated, ovary-intact rats and 2285 ng/ml in E2-treated, ovariectomized ACI rats. These data indicate that estrogen-induced hyperprolactinemia is not the sole factor leading to development of mammary cancers in the E2-treated ACI rat.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-6805, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Shull
authors.forename: T J
authors.initials: TJ
authors.lastname: Spady
authors.forename: M C
authors.initials: MC
authors.lastname: Snyder
authors.forename: S L
authors.initials: SL
authors.lastname: Johansson
authors.forename: K L
authors.initials: KL
authors.lastname: Pennington
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000473:pathology; D011388:Prolactin / Q000097:blood; D051381:Rats; D011912:Rats, Inbred ACI
chemical_list: D004958:Estradiol; D011388:Prolactin