HIGH INHIBITORY ACTIVITY OF A NEW ANTIESTROGEN, RU-16117 (11-ALPHA-METHOXY ETHINYL ESTRADIOL), ON DEVELOPMENT OF DIMETHYLBENZ(A)ANTHRACENE-INDUCED MAMMARY-TUMORS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (1) , 76-81
Abstract
From the 1st day of dimethylbenzanthracene administration, daily treatment with 8 or 24 .mu.g of the new antiestrogen 11.alpha.-methoxy ethinyl estradiol (RU 16117) 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 .mu.g 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 reduced. The levels of receptors for estradiol, progesterone and prolactin in tumor tissue were reduced after treatment with 2.0 .mu.g 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 .mu.g RU 16117, plasma prolactin levels increased in animals receiving the highest dose of the antiestrogen. The potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at the hypothalamic-pituitary and tumor (mammary gland) levels, action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.