Localization and temporal regulation of tissue inhibitor of metalloproteinases-4 in mouse ovary
Localization and temporal regulation of tissue inhibitor of metalloproteinases-4 in mouse ovary
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DOI：
10.1530/rep.1.00810
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发表时间：
2006-06-01
期刊：
影响因子：
3.8
通讯作者：
Duan, Enkui
中科院分区：
文献类型：
--
作者：
Bu, Shumin;Cao, Chenfu;Duan, Enkui
金属蛋白酶组织抑制剂（TIMPs）是卵巢组织重塑的潜在调节因子。本研究的目的是研究TIMP-4蛋白在小鼠卵巢中的定位和时间调控。采用诱导超排卵模型（eCG/hCG）在未成熟小鼠中评估TIMP-4蛋白在卵泡期、排卵前期和黄体寿命期间收集的卵巢中的表达谱。免疫荧光结果显示，TIMP-4蛋白定位于窦卵泡和排卵前卵泡的卵泡膜及邻近的卵巢间质。在用hCG开始黄体化后，在黄体化颗粒细胞内观察到TIMP-4，并在黄体的整个寿命期间持续存在。在周期性卵巢中，TIMP-4信号定位于先前发情周期的黄体，排卵前卵泡的卵泡膜，并且在新形成的黄体中似乎较低。Western分析进一步显示，TIMP-4在颗粒细胞黄体化过程中显著升高，但在各黄体期之间无显著变化。利用体外模型鉴定了TIMP-4表达的假定调节机制。用hCG处理培养的颗粒细胞显著增加TIMP-4蛋白表达水平。总之，我们的数据表明，颗粒细胞的黄体化过程中与TIMP-4的上调，TIMP-4可能在维持黄体功能在整个生命周期的黄体发挥重要作用。
Tissue inhibitors of metalloproteinases (TIMPs) are potential regulators of tissue remodeling in the ovary. The aim of the present study was to examine the localization and temporal regulation of TIMP-4 protein in the mouse ovary. An induced superovulation model (eCG/hCG) was employed in immature mice to evaluate TIMP-4 protein expression profiles in ovaries collected during the follicular phase, the pre ovulatory period, and the luteal lifespan. Immunofluorescence results indicated that TIMP-4 protein was localized to theca of both antral and preovulatory follicles and adjacent ovarian stroma. After the initiation of luteinization with hCG, TIMP-4 was observed within the luteinizing granulosa cells and persisted throughout the lifespan of the corpus luteum. In the cycling ovary, TIMP-4 signaling localized to corpus luteum from previous estrous cycles, the theca of preovulatory follicles, and appeared to be lower in newly forming corpus luteum. Western analysis further showed that the levels of TIMP-4 increased significantly during the luteinization process of granulosa cells, but no significant change was found among all corpus luteum stages. A putative regulatory mechanism of TIMP-4 expression was identified utilizing an in vitro model. Treatment of cultured granulosa cells with hCG significantly augmented TIMP-4 protein expression levels. Together our data indicate that the luteinization process of granulosa cells is associated with up-regulation of TIMP-4 and that TIMP-4 might play an essential role in maintenance of the luteal function during the whole lifespan of corpus luteum.