Dietary energy restriction abolishes development of prolactin-producing pituitary tumors in Fischer 344 rats treated with 17-βestradiol

✍ Scribed by Thomas J. Spady; Athena M. Lemus-Wilson; Karen L. Pennington; Darcy J. Blackwood; Tanya M. Paschall; Diane F. Birt; Rodney D. McComb; James D. Shull

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 376 KB
• Volume: 23
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199810)23:2<86::aid-mc5>3.0.co;2-5

✦ Synopsis

Reduction in energy consumption is known to inhibit development of a variety of spontaneous, carcinogeninduced, and hormone-dependent cancers, but the mechanism or mechanisms by which this occurs remain unknown. We hypothesize that energy consumption may modulate development of estrogen-dependent neoplasms by altering the manner in which target cells respond to estrogens. To test this hypothesis, ovariectomized female Fischer 344 rats were fed diets that allowed consumption of different amounts of energy, and the ability of 17β-estradiol (E2), administered for 10 wk from subcutaneous Silastic implants, to promote development of prolactin-producing pituitary tumors was examined. A 40% restriction of energy consumption virtually abolished the ability of E2 to promote development of pituitary tumors and associated hyperprolactinemia. A 25% restriction of energy consumption appeared to slightly inhibit E2-induced pituitary growth and hyperprolactinemia, but the observed degree of inhibition was not statistically significant. Interestingly, dietary energy restriction did not inhibit induction by E2 of pituitary cell proliferation and lactotroph hyperplasia. Furthermore, E2 treatment inhibited expression of testosterone-repressed prostate message-2 mRNA, a cellular marker of apoptosis, and this inhibitory effect of E2 was blocked by 40% energy restriction. These data suggest that dietary energy restriction virtually abolished E2-induced development 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 modulate estrogen action at the level of the target cell.