Prolactin-immune interactions in carcinogen-induced rat mammary tumors.
Because many mammary tumors are prolactin (PRL) dependent, tumor-bearing 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) PRL cells in the pituitary; b) pituitary PRL as detected by radioimmunoassay (RIA), Nb2 bioassay, and induction of interleukin-2 receptors on splenocytes; c) induction of IL-2R on lymphocytes in response to a standard PRL; d) CD phenotype of the splenocytes and tumor infiltrating lymphocytes. We found that 80% of all NMU-treated animals developed mammary tumors 10 to 13 weeks post-injection. PRL cell number, size, and granule content were unaffected. When tested by RIA or by the Nb2 bioassay, there appeared to be approximately 50% less PRL secreted (2 weeks post-injection) by cells of the NMU-treated than the vehicle-treated animals. However, when tested by IL-2R assay, PRL cells of NMU-treated animals secreted 50% more activity. Splenocytes from the treated animals, 2-6 weeks post-injection, expressed fewer IL-2R in response to standard PRL. NMU treatment (12 wks post-injection) increased the numbers of T-cytotoxic cells by 49%, had no effect on T-helpers, and increased the number of IL-2R positive splenocytes by 81%. Our interpretation is that NMU treatment interferes with the feedback of lymphokines on 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 splenocytes, and thus changes the composition and function of the immune system.
Mukherjee
P
P
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802.
Hauser
U
U
Mastro
A M
AM
Hymer
W C
WC
D000818:Animals; D002273:Carcinogens; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000187:drug effects / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008770:Methylnitrosourea; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011388:Prolactin / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002273:Carcinogens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D008770:Methylnitrosourea; D011388:Prolactin; D013006:Growth Hormone