The effects of the selective estrogen receptor modulators MPP and raloxifene in normal and cancerous human and murine uterine tissue

The goal of this research was to determine the in vitro and in vivo effects of the Selective Estrogen Receptor Modulators (SERMs), methyl-piperidino-pyrazole (MPP), raloxifene, ICI 182,780 and 17β-estradiol on endometrial carcinoma cells in culture and on murine uterine tissue. These SERMs have been developed to target and understand the role of estrogen receptor action in estrogen-responsive organs. Based on their antagonistic actions, SERMs have both real and potential value in treating estrogenresponsive cancers, including endometrial cancer. The studies described herein verify that the SERMs MPP and raloxifene demonstrate partial agonistic effects in ovariectomized wild-type and ER-β knockout (ERβKO) mice but also induce apoptosis and proliferation in vitro in cultured endometrial cell lines, Ishikawa and RL-95. Thus, MPP and raloxifene exert apparently contrasting in vitro and in vivo effects due to their mixed agonist/antagonist action on murine uterine estrogen receptor in vivo. In addition to these data, I report gene expression changes in the uterus of mice treated individually or with the combination of 17β-estradiol and the SERMs, MPP, raloxifene, ICI 182,780 are