Spady T J, Pennington K L, McComb R D, Birt D F, Shull J D
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Mol Carcinog. 1999 Dec;26(4):239-53.
We have demonstrated that a 40% restriction of dietary energy consumption virtually abolishes the development of prolactin (PRL)-producing pituitary tumors in Fischer 344 (F344) rats treated chronically with estrogen, apparently by inhibiting the ability of estrogen to enhance survival within a rapidly proliferating lactotroph population. The purpose of the study reported here was to determine whether energy restriction exerts a similar antitumorigenic action in another rat strain, August x Copenhagen-Irish (ACI), in which PRL-producing pituitary tumors develop in response to estrogen treatment. Ovariectomized female ACI rats were either allowed to consume a control diet ad libitum or were fed a modified diet that restricted energy consumption by 40% relative to the amount of energy consumed by animals fed the control diet. We also examined the ability of 17beta-estradiol (E2) administered for 20 wk via subcutaneous Silastic implants to induce development of PRL-producing pituitary tumors. Treatment with E2 increased pituitary weight as well as the pituitary weight-to-body weight ratio and induced gross hyperprolactinemia to the same extent in ACI rats fed either the control or the energy-restricted diet. Moreover, dietary energy restriction did not affect the ability of E2 to induce pituitary cell proliferation or inhibit apoptosis, as evidenced by quantification of two surrogate markers. These data provide compelling evidence that a 40% restriction of energy consumption does not inhibit the ability of E2 to induce pituitary tumor development in the ACI rat. In conjunction with our published studies of the F344 rat strain, the data presented herein indicate that the inhibitory effects of dietary energy restriction on estrogen-induced pituitary tumor development are rat-strain specific and suggest that sensitivity to specific antitumorigenic actions of energy restriction is strongly affected by genetic background.
我们已经证明，在长期接受雌激素治疗的Fischer 344（F344）大鼠中，饮食能量消耗限制40%实际上可消除催乳素（PRL）分泌性垂体瘤的发生，这显然是通过抑制雌激素增强快速增殖的催乳细胞群体中细胞存活的能力来实现的。本文报道的这项研究的目的是确定能量限制在另一种大鼠品系——奥古斯特×哥本哈根-爱尔兰（ACI）大鼠中是否具有类似的抗肿瘤作用，在该品系中，PRL分泌性垂体瘤会在雌激素治疗后发生。将卵巢切除的雌性ACI大鼠分为两组，一组随意食用对照饮食，另一组喂食改良饮食，该改良饮食相对于食用对照饮食的动物所消耗的能量，将能量消耗限制40%。我们还研究了通过皮下硅橡胶植入物连续20周给予17β-雌二醇（E2）诱导PRL分泌性垂体瘤发生的能力。在喂食对照饮食或能量限制饮食的ACI大鼠中，E2治疗均使垂体重量以及垂体重量与体重之比增加，并诱导出现明显的高催乳素血症，且程度相同。此外，通过对两个替代标志物的定量分析表明，饮食能量限制并不影响E2诱导垂体细胞增殖或抑制细胞凋亡的能力。这些数据提供了令人信服的证据，即能量消耗限制40%并不会抑制E2在ACI大鼠中诱导垂体瘤发生的能力。结合我们已发表的关于F344大鼠品系的研究，本文所呈现的数据表明，饮食能量限制对雌激素诱导的垂体瘤发生的抑制作用具有大鼠品系特异性，并提示对能量限制的特定抗肿瘤作用的敏感性受到遗传背景的强烈影响。
