This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kelly, P. A. Articles by Labrie, F. Search for Related Content PubMed PubMed Citation Articles by Kelly, P. A. Articles by Labrie, F.

High Inhibitory Activity of a New Antiestrogen, RU 16117 (11-Methoxy Ethinyl Estradiol), on the Development of Dimethylbenz(a)anthracene-induced Mammary Tumors

Medical Research Council Group In Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Québec G1V 4G2, Canada [P. A. K., J. A., M. G. C., F. L.], and Centre de Recherches Roussel-UCLAF, Romainville 93230[J-P. R.], France

From the first day of dimethylbenzanthracene administration, daily treatment with 8 or 24 µg of the new antiestrogen 11-methoxy ethinyl estradiol (RU 16117) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after dimethylbenzanthracene administration). At daily doses of 0.5 and 2.0 µg RU 16117, the tumor incidence was reduced to 78.6 and 40.0%, respectively. Not only was the number of animals developing tumors reduced after injection of low doses of RU 16117, but the number of tumors per rat and the size of tumors were also markedly reduced. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 µg RU 16117, while the binding of growth hormone and insulin was not affected. Whereas plasma luteinizing hormone levels decreased after treatment with 8 or 24 µg RU 16117, plasma prolactin levels slightly increased in animals receiving the highest dose of the antiestrogen. It is thus likely that the potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at both the hypothalamic-pituitary and the tumor (mammary gland) levels, the action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.

¹ Associate of the Medical Research Council of Canada.

Received 2/ 3/76. Accepted 10/ 4/76.