Induction of Pituitary and Mammary Tumors in Male, "Fale" and Female Rats by Either DMBA, Estradiol Implant or Combined Treatment

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Abstract
Implanting silastic capsules containing estradiol (E2) into castrated female and fale rats 5 days before 7,12-dimethyl benz(a)anthracene (DMBA) injection increased the incidence of mammary tumors from 0-44.4% and 30%, respectively. This E2 potentiating effect on DMBA-induced mammary tumors was not detected in intact female or male rats, but the incidence of mammary tumors was much lower in intact male rats than in intact female rats with or without E2 implants. Most rats receiving E2 implants developed prolactin secreting pituitary tumors within 100 days after implantation. Serum estrogen level of rats bearing E2 implants in different groups was maintained between 118.3 pg/ml and 194.1 pg/ml. These estrogen levels were not significantly different from that of normal cycling rats at proestrus. The pituitary tumors induced by E2 implants secreted huge amounts of prolactin as revealed by enormous levels of PRL in blood, but normal levels of blood FSH and LH were determined. A clear-cut decrement of blood prolactin levels was measured when .alpha.-bromoergocriptine was given to female rats with or without pituitary tumors. An unexpected induction of prolactin secreting pituitary tumors in rats by maintaining with silastic implant constant blood proestrus estrogen concentrations was clearly demonstrated.