Role of estrogen and prolactin in the growth and receptor levels of N-nitrosomethylurea-induced rat mammary tumors

Abstract

Forty-eight of 81 (59%) of N-nitrosomethylurea-induced rat mammary tumors regressed in average to almost one-half of the original size 10 days after ovariectomy (ovax) (hormone responsive), while 33 remained essentially unchanged (hormone resistant). AT 20 days after ovax, further decline in hormone-responsive tumors was observed when the rats were treated daily with 0.9% NaCl solution on the tenth day after ovax. Treatment for the same length of time with estrogen either alone or in combination with bromocryptine (to effectively suppress serum prolactin level) prevented tumor regression in hormone-responsive tumors. A similar effect was observed when rats were treated with perphenazine (to stimulate endogenous prolactin secretion) either alone or in combination with the antiestrogen tamoxifen. Estrogen receptors (ERs) significantly declined after ovax. Treatment with estrogen or perphenazine did not have any significant effect on ER level. Progesterone receptors (PGRs) became virtually undetectable after ovax. Treatments with estrogen, estrogen plus bromocryptine, and perphenazine plus tamoxifen but not perphenazine alone were able to partially restore PGRs although this effect was of borderline statistical significance. ER and PGR levels were not significantly different between hormone-responsive and -resistant tumors within each group. We conclude that both estrogen and prolactin play a role in the growth of the N-nitrosomethylurea-induced rat mammary tumor. Changes in ER and PGR levels did not correlate with tumor growth under the present experimental conditions.