Tamarkin L, Cohen M, Roselle D, Reichert C, Lippman M, Chabner B
Cancer Res. 1981 Nov;41(11 Pt 1):4432-6.
The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.
研究了松果体激素褪黑素以及松果体切除对用7,12 - 二甲基苯并(α)蒽(DMBA)处理的斯普拉格 - 道利大鼠乳腺腺癌发病率的影响。褪黑素（2.5毫克/千克）与DMBA（5毫克）处理在同一天开始，每天下午给药，持续90天，显著降低了乳腺肿瘤的发病率，从79%（对照组）降至20%（处理组）（p小于0.002）。20日龄时进行松果体切除，50日龄时用7毫克DMBA处理的大鼠，与对照动物（22%）相比，肿瘤发病率更高（88%）。15毫克DMBA导致更高的肿瘤发病率，缩小了松果体切除大鼠与对照动物之间的差异。褪黑素仅部分逆转了松果体切除的影响，将发病率从87%（仅松果体切除）降至63%（松果体切除加褪黑素）；然而，未进行松果体切除、接受褪黑素处理的动物的肿瘤发病率仍然较低（27%）。对接受DMBA处理的无肿瘤和有肿瘤动物的血浆催乳素、促黄体生成素、促卵泡激素、雌二醇和皮质醇进行评估发现，与接受赋形剂处理的动物[65±8纳克/毫升]相比，接受褪黑素处理的动物血浆催乳素浓度显著降低[27±5（标准误）纳克/毫升]。与接受赋形剂处理的松果体切除大鼠（101±13纳克/毫升）相比，接受褪黑素处理的松果体切除大鼠血浆催乳素浓度较低（55±10纳克/毫升）。其他激素不受褪黑素处理的影响。这些数据支持这样的假设，即褪黑素抑制大鼠中DMBA诱导的乳腺肿瘤的发展，而切除松果体则刺激此类肿瘤发展。此外，这些实验提供了证据表明这些作用可能是通过抑制血浆催乳素水平介导的。
