Prostaglandin regulation of murine mammary tumor virus production: a basis for some of the glucocorticoid and prolactin actions on mammary tumor cell cultures.
Hormonal regulation of mouse mammary tumor virus (MuMTV) production has been studied in cell cultures derived from mammary carcinomas of GR mice. The purpose of this study was to define the role of prolactin in dexamethasone-induced MuMTV production and to evaluate the mechanism(s) of action of these hormones. Results of our investigations in vitro establish a central role for prostaglandins, in particular PGF2 alpha. Prolactin treatment up to 1000 ng/ml increased the MuMTV production only slightly when added alone but a maximal stimulatory response was expressed when prolactin was added simultaneously with dexamethasone 2 micrograms/ml. This prolactin-related enhancement of MuMTV production was probably mediated by PGs since it was inhibited by indomethacin, an inhibitor of prostaglandin synthesis. When higher concentrations of indomethacin were used in dexamethasone-treated cultures, MuMTV production, although inhibited, was restored in part by addition of exogeneous PGF2 alpha. PGF2 alpha added alone stimulated the MuMTV production and, in combination with dexamethasone, showed a synergistic effect on stimulation of MuMTV production. Two compounds, PGF2 alpha and TXA2 (measured as TXB2), were produced in significant concentrations by these cultures. These findings suggest that PGF2 alpha exerts a regulating role on production of MuMTV in GR cells and indicate that the actions of both dexamethasone and prolactin are mediated at least in part by prostaglandins.
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000382:microbiology*; D008324:Mammary Tumor Virus, Mouse / Q000254:growth & development*; D051379:Mice; D011388:Prolactin / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011460:Prostaglandins F / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D011453:Prostaglandins; D011460:Prostaglandins F; D013929:Thromboxane B2; D003907:Dexamethasone; D011388:Prolactin; D007213:Indomethacin