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Impeding Estrogens and the Etiology of Breast Cancer¹

Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118

The partial agonistic role of impeding estrogens is further described. Synthesis of progesterone receptor, induced with estradiol, is inhibited by appropriate doses of estriol or 16-epiestriol. Inhibition of 7,12-dimethylbenz(a)anthracene-induced rat breast tumors by estriol was observed. Silastic tubing implants containing estriol markedly reduced tumor takes and delayed onset of first tumors. Experiments are described that suggest different physiological functions for estradiol and estriol. Administration to pregnant rats of antibody specific to estradiol or estriol during Days 11 to 14 of gestation resulted in a slight reduction in the number of offspring for antiestradiol antibody but a nearly total loss of fetuses with antiestriol antibody. As in previous experiments with estriol, the contraceptive function of estriol cyclopentyl ether was found to be reversible when small doses of estradiol were injected on Day 4 of pregnancy. The effect of 2-hydroxyestrone was examined for its antiimplantational and estrogenic activity. No systemic activity was observed up to 500 µg of steroid, but topical activity, following insertion of Silastic tubing implants in rabbit uteri, produced complete contraceptive effects, as compared to 0.9% NaCl solution-containing implants in the contralateral horn. Multiple injections of 50 µg 2-hydroxyestrone resulted in maximal uterine growth in immature and adult ovariectomized rats. The evidence presented suggests that estriol, while containing some estrogenic properties, must have a significantly different physiological role in cancer and reproduction when present in an appropriate admixture with estradiol.

¹ Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md. These studies were supported by Research Grants CA-03135, CA-18226, and CA-18837 from the National Cancer Institute, and Research Grant HD-06799 from the National Institute of Child Health and Human Development, as well as grants from Aids for Cancer Research, Boston, Mass.

² To whom requests for reprints should be addressed.