DIETARY ENERGY RESTRICTION ABOLISHES DEVELOPMENT OF PROLACTIN-PRODUCING PITUITARY-TUMORS IN FISCHER-344 RATS TREATED WITH 17-BETA-ESTRADIOL

Reduction in energy consumption is known to inhibit development of a v ariety of spontaneous, carcinogen-induced, and hormone-dependent cance rs, but the mechanism or mechanisms by which this occurs remain unknow n. We hypothesize that energy consumption may modulate development of estrogen-dependent neoplasms by altering the manner in which target ce lls respond to estrogens. To test this hypothesis, ovariectomized fema le Fischer 344 rats were fed diets that allowed consumption of differe nt amounts of energy, and the ability of 17 beta-estradiol (E2), admin istered for 10 wk from subcutaneous Silastic implants, to promote deve lopment of prolactin-producing pituitary tumors was examined. A 40% re striction of energy consumption virtually abolished the ability of E2 to promote development of pituitary tumors and associated hyperprolact inemia. A 25% restriction of energy consumption appeared to slightly i nhibit E2-induced pituitary growth and hyperprolactinemia, bur the obs erved degree of inhibition was not statistically significant. Interest ingly, dietary energy restriction did not inhibit induction by E2 of p ituitary cell proliferation and lactotroph hyperplasia. Furthermore, E 2 treatment inhibited expression of testosterone-repressed prostate me ssage-2 mRNA, a cellular marker of apoptosis, and this inhibitory effe ct of E2 was blocked by 40% energy restriction. These data suggest tha t dietary energy restriction virtually abolished E2-induced developmen t of prolactin-producing pituitary tumors, not by blocking the ability of E2 to induce cell proliferation but rather by blocking the ability of E2 to enhance cell survival. This study and the accompanying paper provide the first indication that dietary energy consumption may modu late estrogen action at the level of the target cell. (C) 1998 Wiley-L iss, Inc.