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Long-Term Effects of Prenatal and Neonatal Administration of 5ß-Dihydrotestosterone on Normal and Neoplastic Mammary Development in Mice¹

Pharmacology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104 [R. Y., H. N.], and Zoological Institute, Faculty of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113 [T. M.], Japan

The long-term effects on mammary glands of 5ß-dihydrotestosterone, considered to be biologically inactive, were studied in female SHN mice with mammary tumor virus. 5ß-Dihydrotestosterone was administered to mothers for 4 days from Day 12 to Day 15 of pregnancy (prenatal treatment) and to pups for 5 days of postnatal life (neonatal treatment) at daily doses of 1 mg and 200 µg, respectively. Neonatal treatment resulted in marked stimulation of spontaneous mammary tumorigenesis; all neonatally treated mice had palpable mammary tumors by 6.2 months of age, when mammary tumor incidences in the control mice and in mice treated prenatally with 5ß-dihydrotestosterone were 21.1 and 6.3%, respectively. Furthermore, neonatal treatment promoted normal and preneoplastic mammary growth and pituitary prolactin secretion and induced ovarian anovulatory syndrome in all mice. Prenatal treatment also increased the number of mammary hyperplastic alveolar nodules and induced a delayed anovulatory syndrome. These results have demonstrated that perinatal treatment with 5ß-dihydrotestosterone can induce such irreversible changes in the mammary glands, pituitary gland, ovaries, and genital tracts as those seen with other biologically active steroid hormones.

¹ This work was supported in part by Grant-in-aid 101089 for Cancer Research from the Ministry of Education, Science and Culture, Japan.

Received 2/ 3/77. Accepted 9/ 7/77.