PINEAL MELATONIN INHIBITION OF TUMOR PROMOTION IN THE N-NITROSO-N-METHYLUREA MODEL OF MAMMARY CARCINOGENESIS - POTENTIAL INVOLVEMENT OF ANTIESTROGENIC MECHANISMS INVIVO
PINEAL MELATONIN INHIBITION OF TUMOR PROMOTION IN THE N-NITROSO-N-METHYLUREA MODEL OF MAMMARY CARCINOGENESIS - POTENTIAL INVOLVEMENT OF ANTIESTROGENIC MECHANISMS INVIVO
复制标题
DOI：
10.1007/bf01613283
复制
发表时间：
1991-01-01
影响因子：
3.6
通讯作者：
WISE, ME
中科院分区：
文献类型：
--
作者：
BLASK, DE;PELLETIER, DB;WISE, ME
激素反应性大鼠乳腺癌发生的 N-甲基-N-亚硝基脲 (NMU) 模型用于验证松果体主要激素褪黑激素 (Mel) 通过充当抗促剂而不是抗起始剂来抑制肿瘤发生的假设。每天下午晚些时候注射 Mel（500-mu-g/天），仅限于 NMU 乳腺肿瘤发生的起始阶段，在 20 周内对改变肿瘤生长无效。当 Mel 治疗在 NMU 后推迟 4 周，然后继续进行剩余的推广阶段时，只有肿瘤数量显着低于对照组。然而，当梅尔注射涵盖整个促进阶段时，肿瘤发生率和数量均显着低于对照组。尽管通过松果体切除术消除内源性梅尔信号促进了肿瘤生长，但效果并不具有统计学意义。梅尔或松果体切除术均未改变血清雌二醇水平和肿瘤雌激素受体含量。虽然梅尔治疗未能影响循环催乳素水平，但松果体切除术导致血清催乳素增加两倍。卵巢切除术后雌二醇刺激的肿瘤复发可被 20、100 或 500 μg Mel/天或他莫昔芬（20 μg/天）完全阻断。因此，Mel 似乎是一种抗促激素，在乳腺肿瘤发生模型中可能拮抗雌二醇的促肿瘤作用。
The N-methyl-N-nitrosurea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500-mu-g/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500-mu-g Mel/day or tamoxifen (20-mu-g/day). Thus, Mel appears to be an anti-promoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.