ESTROGEN INDUCTION OF PROLACTIN-PRODUCING PITUITARY-TUMORS IN THE FISCHER-344 RAT - MODULATION BY DIETARY-ENERGY BUT NOT PROTEIN CONSUMPTION

Our laboratory is examining the hypothesis that diet may modulate the ability of estrogens to regulate cell proliferation and survival, eith er of which could affect development of neoplasms in estrogen-responsi ve tissues. In this study, we examined whether the amount of energy an d protein consumed in the diet modulates the ability of the synthetic estrogen diethylstilbestrol (DES) to induce development of prolactin-p roducing pituitary tumors in two strains of rat, Fischer 344 (F344) an d Holtzman, that differ in their propensity to develop pituitary tumor s when treated with estrogens. Male F344 rats treated with DES for 8 w k developed pituitary tumors (defined as grossly enlarged pituitary ma sses that displayed diffuse lactotroph hyperplasia but lacked adenomat ous foci). In contrast, male Holtzman rats displayed only a modest inc rease in pituitary weight in response to DES. Energy consumption but n ot protein consumption modulated DES-induced pituitary tumorigenesis i n the male F344 rat. Relative to that observed in untreated animals, p ituitary weights in F344 rats treated with DES increased 11.2- and 9.2 -fold in animals fed either the control diet or an equicaloric high-pr otein diet, respectively, but only 3.5-fold in animals fed an energy-r estricted diet. In contrast, neither the amount of energy nor protein consumed in the diet affected the modest pituitary growth response of male Holtzman rats to administered DES. Energy restriction had no appa rent effect on pituitary cell proliferation, either basal or DES stimu lated, in these rat strains. We concluded that dietary energy restrict ion inhibits the ability of administered DES to induce pituitary tumor development in the F344 rat by acting at a step after induction of pi tuitary cell proliferation. (C) 1998 Wiley-Liss, Inc.