Regulation of Fas ligand expression by estrogen in normal ovary
Regulation of Fas ligand expression by estrogen in normal ovary
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DOI：
10.1016/s1071-5576(02)00162-4
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发表时间：
2002-07-01
期刊：
影响因子：
--
通讯作者：
Mor, G
中科院分区：
文献类型：
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作者：
Sapi, E;Brown, WD;Mor, G
目的：Fas/Fas配体（FasL）系统在乳腺癌、卵巢癌等对化疗敏感的肿瘤中的临床意义已有报道。然而，只有少数研究调查了其表达的潜在激素调节。在这项研究中，我们评估了FasL的表达在正常的女性生殖周期的正常卵巢组织中，确定潜在的激素，可以调节FasL的expression.METHODS：我们用蛋白质印迹分析，检查FasL的表达在整个自然发情周期的大鼠卵巢。我们采用Western blot和RT-PCR方法研究了FasL在人卵巢上皮细胞和正常卵巢组织中的激素调节作用。FasL蛋白在动情期大量出现，动情后期急剧下降，动情间期进一步下降至极低水平，动情前期缺失。由于FasL在周期性卵巢中的蛋白表达模式与雌激素受体β表达模式相似，我们检测了雌激素对FasL蛋白水平的影响，发现雌激素确实上调了卵巢上皮细胞和正常卵巢组织中FasL蛋白和mRNA水平的表达。此外，我们发现，雌激素诱导的FasL蛋白和mRNA水平的增加可以取消4-羟基他莫昔芬，这表明所观察到的FasL表达的增加是由雌激素receptor. CONCLUSION：我们的研究结果支持这一假设，即正常卵巢中的FasL的表达是卵巢敏感的，并可能在正常卵巢组织的生理学中发挥关键作用。
OBJECTIVE: The clinical significance of the Fas/Fas ligand (FasL) system in hormone-sensitive carcinomas such as breast and ovary has been reported. However, only a few studies have investigated the potential hormonal regulation of its expression. In this study, we evaluated the expression of FasL in normal ovarian tissue during the normal female reproductive cycle with the goal of identifying potential hormones that can regulate FasL expression.METHODS: We used Western blot analysis to examine the expression of FasL in the rat ovary throughout the natural estrous cycle. We employed Western blot and reverse transcriptase-polymerase chain reaction to study hormonal regulation of FasL in human ovarian epithelial cells and normal ovarian tissues.RESULTS: FasL protein expression levels change in the ovary during the female reproductive cycle. FasL protein appeared intensively in estrus, declined sharply in metestrous, further decreased to a very low level in diestrus, and was absent in proestrus. Because the protein expression pattern of FasL in the cycling ovary was similar to the estrogen receptor beta expression pattern, we examined the effect of estrogen on the level of FasL protein and found that estrogen indeed upregulates the expression of FasL protein and mRNA levels in ovarian epithelial cells as well as in normal ovarian tissues. Furthermore, we showed that the estrogen-induced increase in the FasL protein and mRNA levels could be abolished by 4-hydroxytamoxifen, which suggests that the observed increase in FasL expression was mediated by estrogen receptor.CONCLUSION: Our findings support the hypothesis that the expression of FasL in normal ovary is hormonally sensitive and could have a key role in the physiology of normal ovarian tissue.