N-Nitroso-N-Methylurea-Induced Mammary Tumors in the Rat: Role of Prolactin and a Prolactin-Lowering Drug

Female outbred Sprague-Dawley rats bearing N-nitroso-N-methylurea (NMU)-induced mammary tumors received various endocrine therapies 3 months after the first NMU injection. Rats were divided into 5 groups (15-20 rats/group) and received a 4-week treatment as follows: group 1, controls; group 2, ovariectomized; group 3,0.5 mg 2-bromoergocryptine (CB-154) injected sc twice daily; group 4a, pituitary implant under the kidney capsule; and group 4b, CB-154 injected during the last 2 weeks of the experiment in rats bearing a pituitary implant. Castration of rats with established NMU-induced tumors resulted in a decrease in both tumor number and size, but these parameters again started to increase 3 weeks post castration. CB-154 failed to reduce the tumor number but did arrest the increase in tumor size, In the animals with a pituitary implant, both tumor number and tumor size increased progressively at a greater rate than in control animals, whereas the addition of CB-154 (group 4b) stabilized the tumor growth, Ovariectomy (OVX) resulted in a significant decline of steroid receptor levels. Prolactin (PRL) receptor levels were significantly stimulated by the pituitary implant, and CB-154 prevented this increase, The present studies confirmed that NMU-induced mammary tumors are less hormone-dependent (response to OVX) than 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumors, The role of PRL also appears to be less important, at least for established tumors, for NMU-induced mammary tumors than for DMBA-induced mammary tumors.