PROLACTIN-IMMUNE INTERACTIONS IN CARCINOGEN-INDUCED RAT MAMMARY-TUMORS

Because many mammary tumors are prolactin (PRL) dependent, tumor-beari ng animals are immunocompromised, and PRL directly affects the immune system, we examined the endocrine and immune systems of rats initiated with nitrosomethylurea (NMU) to cause mammary tumors. We tested: a) P RL cells in the pituitary; b) pituitary PRL as detected by radioimmuno assay (RIA), Nb2 bioassay, and induction of interleukin-2 receptors on splenocytes; c) induction of IL-2R on lymphocytes in response to a st andard PRL; d) CD phenotype of the splenocytes and tumor infiltrating lymphocytes. We found that 80% of all NMU-treated animals developed ma mmary tumors 10 to 13 weeks post-injection. PRL cell number, size, and granule content were unaffected. When tested by RIA or by the Nb2 bio assay, there appeared to be approximately 50% less PRL secreted (2 wee ks post-injection) by cells of the NMU-treated than the vehicle-treate d animals. However, when tested by IL-2R assay, PRL cells of NMU-treat ed animals secreted 50% more activity. Splenocytes from the treated an imals, 2-6 weeks post-injection, expressed fewer IL-2R in response to standard PRL. NMU treatment (12 wks post-injection) increased the numb ers of T-cytotoxic cells by 49%, had no effect on T-helpers, and incre ased the number of IL-2R positive splenocytes by 81%. Our interpretati on is that NMU treatment interferes with the feedback of lymphokines o n the pituitary with a decrease in the form of PRL detected by the RIA and Nb2 assays and an increase in the form which activates splenocyte s, and thus changes the composition and function of the immune system.