Zhao Weijiang, Shi Zhongfang, Yuan Fang, Li Guilin, Sun Yilin, Zhang Yazhuo, Wang Zhongcheng
Neuroscience Center, Shantou University Medical College, Shantou, Guangdong Province 515041, China Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Folia Histochem Cytobiol. 2010 Jan;48(2):278-83. doi: 10.2478/v10042-010-0023-1.
We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy. Compared with vehicle, long-term treatment of DES significantly reduced rat body weight and increased H+E score, both of which were counteracted by melatonin. Administration of melatonin also reduced the expression of VEGF and MMP-9, although no changes were detected in AQP-1 expression. In rats cotreated with melatonin, the RER loosened and accumulated more secretion granules. We thus concluded that melatonin can modulate the effects of DES on the rat anterior pituitary by downregulating expression of VEGF and MMP-9 and suppressing the release of secretion granules, suggesting a therapeutic potential in estrogen-induced pituitary malfunctions.
我们研究了褪黑素对己烯雌酚（DES）处理的大鼠垂体前叶的抗肿瘤作用。21只雌性Wistar大鼠被随机分为三组：溶剂对照组大鼠、DES处理组大鼠以及从第13周开始联合使用褪黑素的DES处理组大鼠。在16周结束时，对大鼠进行称重并断头以进行形态学研究，包括基于苏木精和伊红（H+E）染色的细胞增殖评分评估、血管生成评估、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）和水通道蛋白-1（AQP-1）的免疫染色以及电子显微镜检查。与溶剂对照组相比，长期给予DES显著降低了大鼠体重并提高了H+E评分，而褪黑素可抵消这两种作用。褪黑素的给药还降低了VEGF和MMP-9的表达，尽管未检测到AQP-1表达的变化。在联合使用褪黑素处理的大鼠中，粗面内质网（RER）疏松且积累了更多分泌颗粒。因此，我们得出结论，褪黑素可通过下调VEGF和MMP-9的表达以及抑制分泌颗粒的释放来调节DES对大鼠垂体前叶的作用，提示其在雌激素诱导的垂体功能障碍中具有治疗潜力。
