Spady T J, Lemus-Wilson A M, Pennington K L, Blackwood D J, Paschall T M, Birt D F, McComb R D, Shull J D
Eppley Institute for Research in Cancer and Allied Diseases, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Mol Carcinog. 1998 Oct;23(2):86-95. doi: 10.1002/(sici)1098-2744(199810)23:2<86::aid-mc5>3.0.co;2-5.
Reduction in energy consumption is known to inhibit development of a variety of spontaneous, carcinogen-induced, 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 17beta-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.
已知能量消耗的减少会抑制多种自发的、致癌物诱导的和激素依赖性癌症的发展，但其发生的一种或多种机制仍不清楚。我们假设能量消耗可能通过改变靶细胞对雌激素的反应方式来调节雌激素依赖性肿瘤的发展。为了验证这一假设，给切除卵巢的雌性Fischer 344大鼠喂食允许消耗不同能量的饮食，并检测从皮下Silastic植入物给药10周的17β-雌二醇（E2）促进催乳素分泌型垂体肿瘤发展的能力。40%的能量消耗限制实际上消除了E2促进垂体肿瘤发展和相关高催乳素血症的能力。25%的能量消耗限制似乎略微抑制了E2诱导的垂体生长和高催乳素血症，但观察到的抑制程度没有统计学意义。有趣的是，饮食能量限制并未抑制E2诱导的垂体细胞增殖和催乳素细胞增生。此外，E2处理抑制了睾酮抑制的前列腺信息-2 mRNA的表达，这是一种细胞凋亡的标志物，而E2的这种抑制作用被40%的能量限制所阻断。这些数据表明，饮食能量限制实际上消除了E2诱导的催乳素分泌型垂体肿瘤的发展，不是通过阻断E2诱导细胞增殖的能力，而是通过阻断E2增强细胞存活的能力。本研究及随附论文首次表明，饮食能量消耗可能在靶细胞水平调节雌激素作用。
