褪黑素抑制由17—β—雌二醇诱发的垂体催乳素瘤的生长

目的：观察整体条件下褪黑素（melatonin,MLT)抑制由17－β－雌二醇（E2）诱发的垂体催乳素（prolactin,PRL)瘤的生长,并初步探讨其作用机制,方法：以雄性Sprague-Dawley大鼠皮下埋植E2药泵,诱发PRL瘤,实验组大鼠分5组,在诱瘤之前每日定时分别皮下注射0．05,0．25,0．50,1．00和2．00mgMLT,共90d,对照组大鼠皮下注射等体积4％乙醇－生理盐水。结果（1）给予0．05,0．25,0．50,1．00和2．00mg MLT处理组PRL瘤重量分别较对照组降低25．91％（P＞0．05）,48．78％（P＜0．01）,36．78％（P＜0．05）,31．04％（P＞0．05）和35．22％（P＜0．05）,（2）Northern Blot分别表明,注射0．05,0．25,0．50mg MLT组PRL瘤细胞PRL mRNA表达水平分别比对照组降低33．67％（P＜0．05）,25．51％（P＜0．05）和41．84％（P＜0．01）,原代培养的PRL瘤细胞原位杂交实验也获得类似结果;（3）激光扫描共聚焦显微镜检测结果显示,0．05,0．25和0．50mg MLT组PRL瘤细胞DNA的相对含量分别较对照组降低40．73％（P＜0．001）,51．15％（P＜）．001）和60．23％（P＜0．001）;（4）紫外分光光度法测定显示,0．05,0．25,0．50,1．00和2．00mg MLT组血浆过氧化脂质水平分别比对照组降低26．45％（P＜0．05）,23．97％（P＜0．05）,47．11％（P＜0．001）,66．12％（P＜0．001）和64．46％（P＜0．001）。其量－效关系的相关系数为－0．8257（P＜0．05）。结论一定剂量的MLT对E2诱发PRL瘤生长由于显著的抑制作用,MLT的这种抑瘤作用可能是通过其抑制RL基因由高达和DNA合成实现的。

Inhibitory effect of melatonin on the development of pituitary prolactin-producing tumors induced by 17-beta-estradiol

OBJECTIVE: To examine the inhibitory effect of melatonin (MLT) on the development of pituitary prolactin-producing tumors (prolactinoma) induced by 17-beta-estradiol (E2), in vivo, and explore MLT's oncostatic mechanisms. METHODS: The prolactinomas were established by implanting E2-laden silastic capsules subcutaneously in Sprague-Dawley male rats. MLT doses 0.05, 0.25, 0.50, 1.00, and 2.00 mg/rat were administrated separately to 5 groups subcutaneously starting seven days prior to tumor induction for 97 days. The matched controls were given equal volumes of 4% alcohol in saline. RESULTS: (1) The prolactinoma weights in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 25.91% (P > 0.05), 48.78% (P < 0.01), 36.78% (P < 0.05), 31.04% (P > 0.05) and 35.22% (P > 0.05) respectively which were lower than that of control group; (2) The PRL mRNA levels of prolactinoma in 0.05, 0.25, and 0.50 mg MLT dose groups were 33.67% (P < 0.05), 25.51% (P < 0.05) and 41.84% (P < 0.01) respectively which were lower than that of control group as estimated by Northern Blot, and the in situ hybridization studies; (3) The DNA contents of prolactinoma in 0.05, 0.25 and 0.50 mg MLT dose groups were 40.73% (P < 0.001), 51.15% (P < 0.001) and 60.23% (P < 0.001) respectively which were lower than that of control group by laser scanning confocal microscopy; (4) Plasma peroxidative lipid contents in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 26.45% (P < 0.05), 23.97% (P < 0.05), 47.11% (P < 0.001), 66.12%(P < 0.001) and 64.46% (P < 0.001) respectively which were lower than that of control group. The correlation coefficient between MLT doses and plasma peroxidative lipid contents was -0.8257 (P < 0.05). CONCLUSIONS: MLT in suitable doses is able to inhibit the development of E2-induced prolactinoma by inhibiting the expression of PRL gene and the DNA synthesis. The link between MLT antioxidative action and its inhibitory effect on development of prolactinoma should be further investigated.