Effect of Pharmacological Doses of Estrogen on Ovary-independent Rat Mammary Carcinoma Containing Estrogen and Progesterone Receptors1

Mammary carcinoma induced in male Sprague-Dawley rats by multiple intragastric intubations of 7,12-dimethylbenz-(a)anthracene showed ovary-independent growth but contained estro gen receptors (ER) and progesterone receptors (Yoshida, Yosh ida, Fukunishi, Sato, Okamoto, and Matsumoto, Cancer Res., 42: 2434-2439, 1982). Transplantable carcinoma (MT6) was obtained from dimethylbenz(a)anthracene-induced mammary carcinoma and then maintained in male rats. MT6 tumors with ER grew equally well in males, females, gonadectomized males, males given injections of bromocryptine (1 mg/day) or lisuride hydrogen maléate(50 /¿g/day),and gonadectomized males re ceiving smaller doses of 170-estradiol (1 to 100 u.g¡2days). However, the growth of MT6 was inhibited markedly by injection of a very large amount of 17/î-estradiol (1 mg/2 days). Although transplanted MT6 tumors were ductal carcinoma with cribriform pattern with ER, tumors recurring after injection with 1 mg 17/8estradiol were found to be spindle cell carcinoma without ER, which could grow equally well in recipients treated with or without 1 mg 170-estradiol. These observations suggest that the growth of ovary-independent MT6 tumors with ER and progesterone receptors is inhibited only by pharmacological doses of estrogens and that the loss of growth-inhibiting effect of pharmacological doses of estrogen on MT6 tumors occurs during high-dose estrogen treatment.